Aim Studies examining the association between mortality and anticholinergic burden in the geriatric population are conflicting and are absent in the Mexican American population. The present study aimed to determine whether higher anticholinergic burden increases mortality in a cohort representative of community‐based older Mexican Americans in the USA. Methods This retrospective cohort database study used the Hispanic Established Populations for the Epidemiologic Study of the Elderly cohort. The primary outcome, mortality, was assessed beginning at the second interview in 1995 until the fifth interview in 2005. Medications were classified for anticholinergic burden according to the modified‐Anticholinergic Drug Scale and were summed across all reported medications creating a measure of total anticholinergic burden. Anticholinergic burden was tested for association with mortality using survival analysis. Results The 1497 older adults reporting medication usage were included. Survival analysis showed a statistically significant (P < 0.05) relationship between anticholinergic burden and increased mortality. Conclusions Anticholinergic burden is associated with increased mortality in Southwestern Mexican American older adults who report taking prescription or non prescription medications. These findings suggest that anticholinergic burden might be a risk factor for mortality in this selected population, with additional studies required to further define the risk. Geriatr Gerontol Int 2016; ••: ••–••.