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BACKGROUND:Peptic ulcer disease (PUD) is a major public health burden significantly impacting the cost of hospitalization in the United States (US). We examined the trends, characteristics, complications, cost, and seasonality of PUD-related hospitalizations from 2000 to 2011. METHODS:With the use of the Nationwide Inpatient Sample from 2000 through 2011, we identified PUD-related hospitalizations using the International Classification of Diseases (ICD-9), 9th Revision, and the Clinical Modification code 531.00 to 534.91 as the principal discharge diagnosis. The total number of hospitalizations for each calendar month of the year were added over a 12-year period, and this number was divided by the number of days in that particular month to obtain the mean hospitalizations per day for each month. RESULTS:The study found that 351,921 hospitalizations with the primary discharge diagnosis of peptic ulcer disease (PUD) occurred in the US between 2000 and 2011. This number dropped significantly from 49,524 to 17,499 between 2000 and 2011, and the rate of PUD-related mortality decreased from 4.3% to 3.1%. The mean age of the study population was 66.2 ± 17.4 years; 52.3% were males, and 56.8% were white. The number of hospitalizations in the US peaked in the spring season (916/day), and reached a nadir in the fall season (861/day). The mean cost of PUD hospitalization increased significantly from $11,755 in 2001 to $13,803 in 2011 (relative increase of 17%; p <0.001). CONCLUSION/CONCLUSIONS:The incidence of PUD and its mortality has decreased significantly in the last decade, but its economic burden on the healthcare system remains high. A seasonal pattern of PUD hospitalization showed a peak in PUD-related admissions in the spring season and a trough in the fall season.