Urban-rural disparity constitutes a major source of health inequity also in high-income countries. This study aimed to compare the distribution of deaths due to medical adverse events across urbanization levels among US hospital inpatients. An open dataset from the National Center for Health Statistics (NCHS) comprised all certified deaths of US inpatients over the period 2010–2019. The urbanization level of each decedent was determined in accordance with the 2013 NCHS Urban-Rural Classification Scheme (large metropolitan, medium or small metropolitan, or nonmetropolitan). The outcome was death due to a medical adverse event (ICD-10 codes Y40—Y84) proportional to total inpatient deaths. The data were standardized for sex, ethnicity, and age, and analyzed with linear mixed models. Of the 8 071907 certified inpatient deaths during the study period, 21 444 (0.27%) were primarily attributed to medical adverse events. Decedents who resided in medium or small metropolitans and nonmetropolitans had approximately 0.5 units higher rate of adverse events per 1000 deaths (corresponding to a relative differece of 20%) when compared to decedents who resided in large metropolitans. Moreover, the urban–rural gradients showed an increasing trend towards the end of the study period, as the difference was found to increase at a rate of approximately 0.1 units per year (3%). There were no statistically significant differences between decedents from medium or small metropolitans and nonmetropolitans. The present findings highlight gradients in adverse event deaths between geographic areas, providing a basis for targeted preventive efforts. Future studies are invited to elucidate the underlying phenomena.