Acute myocardial infarction (AMI) is a common medical condition in our clinical practice that should be treated with appropriate revascularization in a timely manner. Percutaneous revascularization (PR) has been the first-line treatment option when feasible. Limited data is available comparing PR to surgical revascularization (SR) in the AMI setting. Study population was extracted from the 2016 Nationwide Readmissions Data using International Classification of Diseases, tenth edition, clinical modifications/procedure coding system codes for AMI, PR, SR, and procedural complications. Study endpoints included in-hospital all-cause mortality, length of index hospital stay (LOS), stroke, acute kidney injury, bleeding, need for blood transfusion, acute respiratory failure, and total hospital charges. The study identified 45,539 discharges with a principal admission diagnosis of AMI (38.7% ST elevation and 61.3% non-ST elevation) who had either PR or SR as a principal procedure (79.1% PR versus 20.9% SR). Single vessel revascularization was performed in 67.8% (93.1% had PR versus 6.9% had SR, p < 0.01). Multivessel revascularization was performed in 32.2% (64.8% had PR versus 35.2% had SR, p < 0.01). 83% of SR was in the setting of non-ST elevation AMI (NSTEMI). In comparison to SR, PR was associated with higher in-hospital all-cause mortality (3.7% versus 2.2%, p < 0.01), shorter LOS (4.3 versus 11.6 days, p < 0.01), and lower incidence of post-procedural stroke (1.0% versus 1.8%, p < 0.01), acute kidney injury (14.9% versus 24.8%, p < 0.01), bleeding (4.3% versus 47.1%, p < 0.01), need for blood transfusion (2.9% versus 18.5%, p < 0.01), acute respiratory failure (10.7% versus 19.8%, p < 0.01), and total hospital charges (120,590$ versus 229,917$, p < 0.01). These results persist after adjustment for baseline characteristics. In a subgroup analysis, SR mortality benefit persisted in patients who had multivessel revascularization (in both ST and non-ST elevation AMI), but not in single vessel revascularization. In patients presented with AMI, PR was associated with higher in-hospital all-cause mortality but lower morbidity, shorter LOS, and lower total hospital charges than SR. However, the mortality benefit of SR was seen in multivessel revascularization only, and not in single vessel revascularization.