Background: Hospitalization for peptic ulcer disease (PUD) has been described outside of North America as peaking in the fall and winter. However, no recent literature has so far investigated the seasonal fluctuations and complications of PUD in the USA. Study Design: Cross-sectional population database review. Methods: Patients with a diagnosis of either acute gastric or acute duodenal ulcers from January 1, 2015, through December 31, 2017, were identified in the Healthcare Cost and Utilization Project's National Inpatient Sample. The proportion of admissions with either hemorrhage or perforation was determined for each season and further subdivided into geographic regions. Results: Of 18 829 hospitalizations for PUD, admissions were the highest in the fall (25.9%) while being the lowest in the summer (23.9%). Complications, hemorrhage or perforation, were the highest and the lowest in the fall and spring, respectively (75.7% vs. 73.6%; P = 0.060 for comparing all 4 seasons). Geographically, the West had the highest rate of peptic ulcer hemorrhage (64.5%, P = 0.004), while the northeast had the highest rate of perforation (14.3%, P = 0.003). Hemorrhage was more common in males, those who used aspirin, nonsteroidal anti-inflammatory drugs, or anticoagulants, and diabetics (P < 0.05). Perforation was less common in males, those with diabetes, obesity, or hypertension (HTN), or those using aspirin or anticoagulants (P < 0.05). Helicobacter pylori infection was more associated with perforation in the fall and winter months. Conclusion: Seasonal and regional trends in hospitalizations due to PUD may help identify modifiable risk factors, which can improve diagnostic and treatment outcomes for patients by allowing for more targeted identification of vulnerable populations. [ABSTRACT FROM AUTHOR]