Background: Laparoscopic cholecystectomy has gained popularity. The goal of this study was to evaluate outcome differences between open vs laparoscopic cholecystectomy. Method: Using a large NIS database and ICD-9 coding for open vs laparoscopic cholecystectomy, we compared inpatient outcomes for these two procedures regarding the occurrence of myocardial infarctions and mortality using uni- and multivariate analysis by studying 5 years of data from 2010 to 2015. Results: Open cholecystectomy was inferior to laparoscopic procedure with a higher occurrence of non-ST-elevation myocardial infarction (Non-STEMI), ST-elevation myocardial infarction (STEMI), and mortality in comparison to laparoscopic cholecystectomy. For example, using 2010 database, the occurrence of STEMI was 0.2 vs 0% (OR 3.1, CI 1.7-5.5, p<0.001), for Non-STEMI 1 vs 0.4% (OR 2.5 CI 2.0-3.0, p<0001) and for mortality 0.4 vs 0.4% (OR 9.2, CI 7.9-10.6, p<0001). After adjustment for age, obesity, diabetes, and hypertension, the occurrence of STEMI, Non-STEMI, and mortality remained higher in the open cholecystectomy cohort (mortality multivariate OR 6.4, CI 5.5-7.4, p<0001). Conclusion: Open cholecystectomy is associated with a higher rate of STEMI, Non-STEMI, and a markedly higher rate of mortality in comparison to the laparoscopic approach. Our study suggests that laparoscopic cholecystectomy should remain the first choice for patients needing gallbladder surgery.