Background: We compared staged percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) with mitral valve replacement (MVR) in patients with combined single vessel and rheumatic mitral valve disease. Methods: We prospectively evaluated 80 patients with combined single coronary artery (requiring revascularization in non-LAD (Left Anterior Descending artery) territory) and rheumatic mitral valve disease, divided into two groups; Group I consisting of 40 patients who underwent staged PCI, and mitral valve replacement 3 months later, and Group II consisting of 40 patients who underwent combined CABG (using saphenous venous graft) and mitral valve replacement. We compared between both groups. Results: The median aortic cross-clamp and cardiopulmonary bypass times were 44 and 62 minutes for Group I, versus 60.5 and 82 minutes for Group II, that difference between groups is statistically significant. 8 patients (20%) in Group I needed inotropic support versus 12 patients (30%) in Group II, which is not statistically significant. No patients in both groups did need any mechanical support in the form of intra-aortic balloon pump (IABP). None of the patients in both groups had intraoperative ECG (electrocardiogram) changes in the form of ischemia or arrhythmias. The median intensive care unit (ICU) length of stay (hours) and hospital length of stay (days) were 39 hours and 5.5 days for Group I, versus 56.5 hours and 8.5 days for Group II, that difference between groups is statistically significant. The median blood loss (ml) postoperatively was 925 in group I versus 1075 in group II, which is statistically significant. However, the rate of re-exploration for bleeding did not differ significantly between both groups, with 1 case only (2.5%) in group I versus 2 cases (5%) in group II, and no postoperative delayed cardiac tamponade noted in any of the two groups. The post-operative complications for groups I and II included 0 (0%) versus 3 (7.5%) prolonged mechanical ventilation (>24 h), 0 (0%) versus 1 (2.5%) respiratory complications, 0 (0%) versus 2 (5%) wound infection, 0 (0%) versus 1 (2.5%) cerebrovascular accidents, 2 (5%) versus 1 (2.5%) acute kidney injury, respectively. There is no statistically significant difference between both groups regarding these previous post-operative complications. None of the patients in both groups died within the first 30 days after surgery. None of the patients in both groups had major cardiac events or CCU (Cardiac Care Unit) admission. Regional wall motion abnormalities were noted in 15 patients (37.5%) of group I versus 17 patients (42.5%) of group II, who all undergone stress ECG, of whom 9 patients (22.5%) in group I versus 11 patients (27.5%) in group II showed positive results, and qualified for diagnostic coronary angiography, which confirmed the need for reoperation for myocardial ischemia/infarction within the first year of follow up post-operatively in 4 patients (10%) of group I versus 8 patients (20%) of group II. All these follow up outcomes showed no significant difference between both groups. Conclusions: A staged approach of PCI followed by MVR is an alternative to the conventional combined CABG and MVR, can be performed safely in some patients with single coronary artery and MV disease, and is associated with good short and follow-up outcomes