Saints' play-off dream ended in heartache when they lost 4-3 on penalties to Derby.
Trailing 2-1 from the home leg Saints put up a valiant fight and won 3-2 on the night to take the game to extra-time and ultimately penalties.
Darren Moore put Derby ahead before Jhon Viafara equalised almost immediately.
Viafara fired Saints into a second half lead, level on aggregate, but Derby hit back when Leon Best inadvertently turned into his own.
Saints looked to be heading out until sub Grzgeorz Rasiak, a former Derby player, lashed home a shot three minutes from the end of normal time.
Extra-time was a cagey affair with both sides looking tired and the match went to penalties.
Leon Best and Inigo Idiakez were the two men who missed for Saints who now have to face at least another season in the Championship.
The match got off to the most pulsating of starts with two goals in the space of a minute.
Derby took the lead through another direct route after just three minutes.
Matt Oakley swung in a corner from the right and Darren Moore was left with time and space and headed downwards past Rudi Skacel on the post and Kelvin Davis who had got a hand to it to make it 1-0 on the night and 3-1 on aggregate.
It seemed momentarily as if Saints had a mountain to climb.
But it was a lot more achievable when they got one back almost directly from the kick off.
Moore's header back to Stephen Bywater was a little short and the Derby keeper charged outside his box to head clear.
But he only picked out Jhon Viafara who fired a shot from 30 yards that rocketed straight into the empty net.
That made it 1-1 on the night and left Saints still one goal behind on aggregate.
Davis had his first save to make on eight minutes, getting down to his right to push away Steve Howard's zipping low effort from distance.
As the half wore on chances were more limited but Saints were starting to get on top, playing some nice football and keeping the Derby backline occupied.
The biggest threat to Saints was conceding set-pieces where Derby had a clear height advantage over George Burley's men.
Craig Fagan briefly threatened but Skacel kept him out wide and he sliced his effort clear of the near post.
Saints had huge appeals for a penalty turned down when Viafara's cross was blocked by Dean Leacock but referee Andy D'Urso was having none of it.
Seth Johnson was the next man to come close with a low shot from 20 yards which skipped just past the post.
Johnson became the first man in the book just before the break for leaving a foot in on Davis who did well to get down and collect a low ball from the right from Fagan.
When the half time whistle blew the situation was as it was at the start of the game. Saints may not have created many chances in the first half but they still only needed one goal in the second to get back level.
At the start of the second half Saints had Derby pinned back and were piling on the pressure.
Derby were remaining strong at the back but if it continued then a chance would have to come.
And it did and on 54 minutes Viafara took it.
Leon Best did superbly to outmuscle Leacock and spot the run of Viafara on the right.
He played him in and the Colombian rifled the ball in at Bywater's near post to make it 2-1 to Saints on the night and level at 3-3 on aggregate.
And just three minutes later Saints could have got another when a corner broke to Best at the far post but he blazed over.
Derby hit back though and came close to scoring when a low cross across the area made it all the way to Fagan who slid in and crashed his effort against the post.
But Derby did get themselves a goal on 66 minutes.
Johnson swung in a corner and Best won the ball ahead of Giles Barnes at the near post. However, it flicked off him and flew straight at goal and again Skacel was unable to keep it out on the post.
The Rams had their one goal advantage in the tie back and Saints knew they had to score again to keep the dream of Wembley alive.
Burley made a change to try and change things on 72 minutes with Djamel Belmadi replacing the injured Chris Makin. Viafara moved to right back and Belmadi right midfield.
That was followed two minutes later by the introduction of Grzegorz Rasiak for Marek Saganowski.
Saints almost got in when Belmadi found the ball at his feet in the area but he cut inside before shooting and a Derby defender was able to get across and deflect his effort wide.
Burley had one last roll of the dice when he brought on Inigo Idiakez for Danny Guthrie.
And with a minute left Saints got what they so desperately wanted - a goal.
Belmadi charged into the area and was tackled but the ball fell to Rasiak who spun and hit it first time and it flew into Bywater's bottom right hand corner.
Saints were leading 3-2 on the night but it was level at 4-4 on aggregate and heading to extra-time.
Saints so nearly snatched it in injury time when Skacel was played in by a brilliant Rasiak backheel but fired over from the edge of the area.
Shortly after the final whistle went and it was going to extra-time.
Saints had an early scare when Fagan couldn't quite reach a cross at the far post.
Derby were even closer six minutes in when Davis had to parry a Fagan header and it dropped under the bar where Chris Baird was waiting to head behind.
Just before the end of the first half of extra-time David Jones thought he had scored but his shot whistled inches past the post.
Moments later Davis had to turn over the bar after a Howard header from a corner but Saints repelled the danger and the aggregate scores were still level as the teams turned around.
Derby were on top in the second period with tired legs on both teams.
Howard had a good chance when he was picked out by a Jones free kick but put it wide.
Saints worked themselves an opening when Rasiak played in Best but he was tired and took his shot early making it easy for Bywater.
And the game almost inevitably went to penalties.
Shootout: Saints got to take them in front of their own fans and had the first kick.
Saints - Leon Best - miss. Right foot wide of the keeper's left hand post. 0-0 Derby - David Jones - score. Left foot keeper's bottom left. Davis dives the other way. 0-1.
Saints - Andrew Surman - score. Left foot straight down the middle. Keeper dives to the right. 1-1.
Derby - Steve Howard - score. Right foot keeper's top right hand corner. Davis dives the other way. 1-2.
Saints - Rudi Skacel - score. Left foot straight down the middle. Keeper goes to his left. 2-2.
Derby - Giles Barnes - score. Right foot high down the middle. Davis dives to his left. 2-3.
Saints - Grzegorz Rasiak - score. Left foot keeper's bottom right hand corner. Keeper dives the other way, 3-3.
Derby - Jay McEveley - score. Left foot keeper's top left hand corner. Davis goes the right way. 3-4.
Saints - Inigo Idiakez - miss. Right foot over the bar. Derby win 3-4 on penalties.
Teams: Derby: Bywater, Mears, Leacock, Moore, McEveley, Fagan (Currie 105), Oakley, Johnson (Jones 87), Pearson, Macken (Barnes 62), Howard.
Not used: Camp, Edworthy.
Saints: Davis, Makin (Belmadi 72), Baird, Cranie, Skacel, Viafara, Guthrie (Idiakez 84), Pele, Surman, Best, Saganowski (Rasiak 74).
Not used: Bialkowski, Wright-Phillips.
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