Purpose Adverse drug events (ADEs) represent medication-related patient harm, which is associated with significant patient morbidity and mortality. This study was conducted to determine the rate, specific causes, and outcomes of ADE-related hospitalization in the USA. Methods We used the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample dataset for the years 2008 to 2011. We selected patients with ADE based on 537 Classification of Diseases-9 codes. Main outcome measures included yearly prevalence, cost, length of stay, and mortality of ADE-related hospitalizations. Calculations were performed on weighted samples, and statistical significance was set at p-value <0.05 (two-tailed). Results We estimated the total hospitalizations with ADE to be 9 440 757 patients (6.28% of total) from 2008 to 2011. Increasing trend was noted from 2008 (5.97%) to 2011 (6.82%) with an annual percentage change rate of 4.37. Patients with ADE were significantly older (2011: mean age 61.42 vs. 48.65 years) and had more comorbidities. Steroids (14.49%), antineoplastic drugs (13.06%), anticoagulants (11.33%), nonsteroidal anti-inflammatory drugs (8.78%), and opiates/narcotics (6.48%) were the five most common causes of ADE. Patient with ADE stayed 1.89 days [95% confidence interval (CI) (1.79-1.99); p < 0.001] longer, incurred $1851.44 [95%CI ($1613.90-$2088.96), p < 0.001] higher with higher odds of mortality 1.27 [95%CI (1.24-1.29), p < 0.001]. Conclusion Adverse drug event carries a significant burden of inpatient hospital care, incurs more cost, and leads to increased loss of life. Targeted policies to reduce them could potentially help decrease mortality as well as drive down cost. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]