The presence of mitral regurgitation (MR) is associated with an impaired prognosis in patients with ischemic heart disease. However, data with regard to the impact of this condition in patients with ST-segment elevation myocardial infarction (STEMI) treated by means of primary percutaneous coronary intervention (PPCI) are lacking. Our aim was to assess the effect of MR in the long-term prognosis of patients with STEMI following PPCI. We analyzed a prospective registry of 1868 patients (mean age 62±13 years, 79.9% male) with STEMI treated by PPCI in our centre between January 2006 and December 2010. Our primary outcome was the composite end-point of all-cause mortality or admission due to heart failure during follow-up. After exclusions, 1036 patients remained for the final analysis. Moderate or severe MR was detected in 119 patients (11.5%). Those with more severe MR were more frequently female (P<0.001), older (P<0.001) and with lower ejection fraction (P<0.001). After a median follow-up of 2.8 (1.7-4.3) years, 139 patients (13.4%) experienced our primary end-point. There was an association between the unfavourable combined event and the degree of MR (P <0.001). After adjustment for relevant confounders, moderate or severe MR remained as an independent predictor of the combined primary endpoint (Adjusted HR 3.14, CI95% 1.57-6.27), and each event separately (Adjusted HR death 3.1, CI95% 1.34-7.2) (Adjusted HR heart failure 3.3, CI95% 1.16-9.4). In conclusion, moderate or severe MR detected early with echocardiography was independently associated with a worse long-term prognosis in STEMI patients treated with PPCI.