Abstract Background Recent randomized clinical trials have suggested that complete revascularization (CR) instead of culprit-vessel only revascularization (CVO) strategies may take a stand in the optimal management of patients admitted for acute myocardial infarction (AMI) with multivessel (MV) disease undergoing primary percutaneous coronary intervention (P-PCI). However, despite the 2017 ST-elevation acute coronary syndrome (STEMI) guidelines update with a new class of recommendation for CR, it remains controversial whether this strategy leads to better outcomes. Purpose To compare CR versus CV strategies during hospitalization in patients presenting with AMI with multivessel disease at P-PCI. Methods We analyzed data from all patients admitted with non-ST acute myocardial infarction (NSTEMI) and STEMI in a portuguese coronary care unit (CCU), between 2007 and 2016. We then evaluated potential differences of CR versus CVO with PCI during hospitalization in AMI patients with multivessel disease, defined by at least 2 different diseased main coronary vessels, saphenous vein or mammary artery conduits. We used 1:1 ratio propensity score matching to study the impact of CR on patient mortality and adjusted data for relevant risk factors at admission time. Results A total of 4758 patients were admitted for AMI, 2690 NSTEMI (56.5%) and 2068 STEMI (43.5%). Access to PCI records was possible in 3162 (66.5%) patients, of which 1707 (54%) underwent CR versus 1455 (46%) who underwent CVO. CVO patients were older (67.9±11.8 vs. 63.5±13.1 years, p<0.001), more diabetic (56.5% vs. 47.1%, p<0.001), hypertensive (78.4% vs. 72.2%, p<0.001), dyslipidemic (82.1% vs. 75%, p<0.001), had greater GRACE score at admission (mean score 143.4±37.2 vs. 131.2±131.2, p<0.001), had more severe coronary disease (mean number of diseased vessels – 2.56±0.6 vs. 2.18±0.4, p<0.004), reached higher Killip class (mean – 1.42±0.9 vs. 1.26±0.7, p<0.001) and had lower left ventricular ejection fraction (48.07±11.6 vs. 51.25±10.5, p<0.001). No significant differences were found in peak troponin-I release between CR and CV (44.7±69 vs. 46.9±76, respectively, p=0.468). After propensity matching, we obtained 130 CR and 133 CVO patients. In this cohort all-cause mortality was lower in CR group at 6-month (RR 0.262, CI 95% 0.071–0.962, p=0.031) and 1-year (RR 0.340, CI 95% 0.119–0.973, p=0.036) follow-up. When comparing STEMI versus NSTEMI all-cause mortality was nonsignificantly lower in CR (RR 0.394 vs. 0.226, p=0.12 vs. p=0.16). Conclusions In patients presenting with AMI and MV disease, CR strategy during hospitalization leads to greater 6-month and 1-year survival when compared with CVO strategy. Despite not having found significant differences when STEMI was directly compared to NSTEMI, we believe this was due to the great loss of patient numbers after propensity matching, requiring larger trials to prove the effect.