Jose Mourinho famously first made his mark on Europe's top competition at Old Trafford a decade ago when Porto knocked the Red Devils out en-route to winning the title.
Here we pick out five key facts ahead of their tie.
- The last time United and Madrid met was in the 2003 Champions League quarter-finals when the Spanish side progressed 6-5 on aggregate. Brazilian striker Ronaldo scored a hat-trick in the return leg at Old Trafford.
- On the two occasions Jose Mourinho has won the Champions League his side have knocked out English opposition in the last-16. His Porto memorably ousted United in 2003-04 before he steered Inter past former club Chelsea three years ago.
- Mourinho has never won a Champions League game at Old Trafford. Porto's progress was built on a 1-1 draw while Inter lost at United 2-0 in 2008-09.
:- Mourinho has all but given up hopes of winning La Liga this season, describing his side's task as "almost impossible" after they fell 13 points behind leaders Barcelona at the weekend.