Valencia defied the early sending-off of Seydou Keita to beat Ludogorets Razgrad 3-0 away and virtually seal its place in the Europa League quarter-finals on Thursday.
In other last-16 first legs, Jackson Martinez scored Porto's goal in a 1-0 win over Napoli and Basel drew 0-0 at home to Red Bull Salzburg.
Valencia was 1-0 ahead thanks to Antonio Barragan's fifth-minute goal when Keita was given a straight red card for bringing down Roman Bezjak in the penalty box in the 24th.
Bezjak's spot kick was saved and the Spanish visitors added goals by Fede Cartabia in the 33rd and Philippe Senderos in the 59th. Juninho Quixada was sent off with 10 minutes to go for Ludogorets.
There were five more last-16 first legs late Thursday.