Ajax Amsterdam bravely fought back from a goal down to beat Manchester United 2-1 at Old Trafford but still went out of the Europa League, losing 3-2 on aggregate.
Javier Hernandez gave United the perfect start in the last-32 tie when he scored from an inch-perfect pass from strike-partner Dimitar Berbatov to give his side the lead after just six minutes.
But Ajax never looked like giving up and fought back in a pulsating end to end match. Aras Ozbiliz equalised just before half-time to give the Dutch side hope and the visitors maintained their momentum after the break.
Nani hit the bar for United before Ozbiliz turned provider for Ajax defender Toby Alderweireld with three minutes left to play. One more goal would have made it 3-3 on aggregate and sent the Dutch side through on away goals, but United held on.
Ajax became the first Dutch side to win at Old Trafford but United go through and will play Spanish side Athletic Bilbao in the last 16.
Iker Muniain struck as the ten-man of Bilbao claimed a 1-0 win over Lokomotiv Moscow to advance to by virtue of the away goals rule.
Lokomotiv were 2-1 winners in the first leg and seemed content to sit on that result in Spain - a mission that seemed to become significantly easier when Fernando Amorebieta was sent off for a second yellow card on the hour mark.
But just two minutes after his departure, Muniain put the hosts ahead from a corner and Lokomotiv were powerless to get a goal of their own despite having the time and the numerical advantage to do so.
Almost seven months after it began, Stoke's Europa League adventure came to an end in Valencia as Jonas' first-half goal earned the hosts a 1-0 victory at the Mestalla and a 2-0 win on aggregate.
The Potters launched their first European campaign since the 1970s with an away win over Hajduk Split back on August 4 and came through a group containing Besiktas and Dynamo Kiev, winning seven of their 12 games.
It was always an uphill struggle after they lost the home leg last week and, although Kenwyne Jones will look back on two glorious first-half chances, it is Valencia who deservedly go on to a last-16 meeting with PSV Eindhoven, who beat Trabzonspor 6-2 on aggregate.
A brace form Tim Matavz helped Eredivisie leaders PSV to a 4-1 second-leg win at the Philips Stadion. The result was a formality by half-time, with the hosts 3-1 up and Turkish side Trabzonspor reduced to ten men following the sending-off of goalkeeper Tolga Zengin.
The visitors started with hope after a narrow 2-1 loss in Turkey but a 15th-minute Dries Mertens penalty extended PSV's advantage and Matavz and Kevin Strootman extended PSV's lead before Burak Yilmaz pulled one back.
Zengin was sent off one minute before the break for handling the ball outside his area and Matavz rounded off a fine display by the Dutch team when he scored his side's fourth and final goal seven minutes after the break.
Last year's runners-up Braga were knocked out despite a brave bid to overturn a 2-0 first leg deficit. The Portuguese side beat Besiktas 1-0 in Turkey through an early strike by Rodrigo Lima, but lost out 2-1 on aggregate.
Klaas Jan Huntelaar scored a hat-trick including two goals in extra-time as Schalke nudged past Viktoria Plzen 3-1 on the night and 4-2 on aggregate.
Huntelaar had opened the scoring in the seventh minute but Frantisek Rajtoral struck an 88th-minute equaliser for Plzen despite the sending-off of Marek Bakos on the hour.
However, Schalke dominated extra-time and they were rewarded with Huntelaar putting them ahead in the second half before he sealed victory on the stroke of full-time.
Atletico Madrid eased home against Lazio with a 1-0 win on the night giving them a 4-1 aggregate success. Diego Godin scored the only goal early in the second half at the Estadio Vicente.
Ukrainians Metalist Kharkiv completed an emphatic 8-1 aggregate win over Salzburg with a 4-1 win in Kharkiv, while Greek side Olympiakos rounded off a 2-0 aggregate win over Rubin Kazan with a 1-0 second leg win.
Matias Fernandez scored a late winner for Sporting Lisbon against Polish side Legia Warsaw, which was enough to see the Portuguese side 3-2 on aggregate after a 1-0 win on the night.
Udinese shrugged off the disappointment of a goalless first leg in Italy to hammer PAOK Salonika 3-0 in Greece. Danilo opened the scoring after six minutes and Antonio Floro Flores and Maurizio Domizzi sealed an emphatic victory.
Former Manchester United striker Mame Biram Diouf scored the only goal as Hannover won 1-0 in Belgium to complete a 3-1 aggregate triumph over Club Brugge.
Nacer Chadli's 29th-minute effort earned FC Twente a 1-0 win over Steaua Bucharest for a 2-0 aggregate victory, while a goalless draw was good enough for Standard Liege to squeeze past Wisla Krakow 1-1 on aggregate on the away goals rule.
Athletic Bilbao beat Lokomotiv Moscow 1-0 to also advance on away goals after a 2-2 aggregate score. Iker Muniain scored the crucial goal two minutes after Fernando Amorebieta's 60th-minute sending-off.