Manchester United have reached the last 16 of the Europa League in each of the six occasions that they have competed in UEFA's second-tier competition.
Italian giants AC Milan were there most recent opponents at this stage of the 2020/21 edition and were narrowly beaten 2-1 by Ole Gunnar Solskjaer's side on aggregate.
United have also previously played Spanish opposition in this round before, back when they were knocked out against Marcelo Bielsa's Athletic Club in 2012.
Former Manchester City manager Manuel Pellegrini and Real Betis will hope to take encouragement from that feat when heading to Old Trafford for this week's first leg tie.
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