If Real fail to take all three points they can consider themselves out of the LaLiga title race, while Atletico still retain some hope of catching leaders Barcelona.
Here, we take a look at five of their notable past meetings.
Real Madrid 2 Atletico Madrid 1, European Cup semi-final play-off, May 1959
After drawing 2-2 on aggregate over two legs, the Madrid sides contested a third match as a play-off to decide who would tackle French side Reims in the European Cup final. Real had won 2-1 at the Bernabeu and Atletico were 1-0 winners in the second leg, in the days before the away goals rule was a factor.
The play-off was staged at the neutral ground of La Romareda in Zaragoza, and Real won 2-1 with goals from Alfredo Di Stefano and Ferenc Puskas. Real went on to beat Reims 2-0 in the final.
Real Madrid 2 Atletico Madrid 2, LaLiga, January 2003
The points were shared from a bad-tempered clash thanks to a controversial late equaliser from Demetrio Albertini. Real lived to regret a missed penalty from Luis Figo, who failed from the spot when attempting to complete a hat-trick, and Los Blancos were infuriated by a free-kick going against them in the lead-up to the Atletico leveller.
Real defender Ivan Helguera and Atletico’s Jose Garcia Calvo were both sent off in the draw, which allowed Real Sociedad to take a three-point lead at the top of the table. Real Madrid, however, went on to take the title.
Real Madrid 4 Atletico Madrid 1 (after extra time), Champions League final, May 2014
Lisbon hosted a rare occasion of two teams from the same city meeting in Europe’s elite club competition final. Sergio Ramos’ dramatic stoppage-time header brought Real back into a game they had trailed in since the 36th minute, taking the match into an extra 30 minutes.
Despite keeping Real at bay in the first 15 minutes of extra-time, a tired Atletico were blown away in the closing stages, conceding strikes from Gareth Bale, Marcelo and a Cristiano Ronaldo penalty.
Real Madrid 2 Atletico Madrid 2, Copa del Rey round of 16 second leg, January 2015
Atletico took a 2-0 win from their then Vicente Calderon home to the Bernabeu, but rather than sit on the first-leg lead they went for more goals. Fernando Torres scored inside a minute, and incredibly he repeated the trick at the start of the second half.
Ramos had pulled Real level before half-time, and Ronaldo soon responded to the second goal from Torres with a header, but Atletico triumphed 4-2 on aggregate. Their cup euphoria was short-lived though, as Atletico lost by the same margin to Barcelona in the next round.
Real Madrid 1 Atletico Madrid 1 (Real Madrid won 5-3 on penalties), Champions League final, May 2016
They met again in the Champions League final in 2016, with San Siro the venue this time. Ramos scored a 15th-minute opener despite a suspicion of offside, but Belgian winger Yannick Carrasco stepped off the bench to level up for Atletico late in the second half.
The extra-time period proved unusually quiet before the match was settled by penalties. Juanfran hit a post with Atletico’s fourth, giving Ronaldo the chance for glory as his spot-kick sealed Real’s 11th Champions League title.
Provided by Press Association Sport
