Introduction: Influence of gender in the epidemiology of acute pancreatitis (AP) has been previously reported. We aim to analyze gender based differences of AP hospitalizations in the US over the past decade. We hypothesize that men with AP are likely to develop severe complications and have a higher in-hospital mortality rate. Methods: Between 2005 to 2012, data was extracted from the National Inpatient Sample on adult (Age>18 years) patients with AP (ICD 9 CM: 577.0). Exclusion criteria was applied for chronic pancreatitis and other pancreatic and biliary disorders (ICD 9 CM: 577.1, 577.8, 577.9, 157.0, 157.1, 157.2, 157.3, 157.4, 157.8, 157.9, 155.0, 155.1, 155.2,156.0, 156.1, 156.2, 156.8. 156.9). Using multivariate logistic regression, in-hospital mortality, comorbidities, complications and procedure rates were compared between the men and women with AP (SAS version 9.3). Results: During the study period, 293,165 women and 286,573 men with acute pancreatitis were admitted to the US hospitals, with a ratio of 1.03:1. Men admitted for AP had increased number of comorbidities: DM (P<0.0001), Hypertension (P<0.0001), Hyperlipidemia (P<0.0001) and CAD (P<0.0001). Men were more likely to be smokers (23.9% vs.15.6%, P<0.0001) and had history of drug abuse (33.6% vs.19.6%, P<0.0001) and alcohol abuse (19.7% vs. 7.2%, P<0.0001). Women were more likely to have biliary tract disorders (39.3% vs 26.8%, P<0.0001). Men were more likely to be evaluated by CT (2.9% vs 2.7%, P<0.0001) while women were more likely to undergo Ultrasound (1.6% vs. 1.5%, P=0.02) and MRCP (1.2% vs. 0.9%, P<0.0001). Men were more likely to develop septic shock (2.2% vs 1.8%, P<0.0001), ARDS (5.2% vs. 3.9%, P<0.0001) and required more intubation (4.3% vs. 3.0%, P<0.0001). Women were more likely to undergo biliary intervention (cholecystectomy, biliary stenting, ampullary surgery). More men received enteral nutrition (1.2% vs. 0.9%, P<0.0001) while more women received TPN (2.6% vs. 2.4%, P<0.0001). Men with AP had a higher in-hospital mortality rate (2.8% vs. 2.4%, P<0.0001). Conclusion: Men are more likely to be hospitalised with alcoholic pancreatitis and women are more likely to be hospitalized with biliary pancreatitis. Men with AP are likely to develop severe complications leading to higher in-hospital mortality when compared with women. Men with AP may benefit from more intensive treatment at the onset for better outcome.