OBJECTIVE Among selective serotonin reuptake inhibitors (SSRIs), paroxetine is strongly anticholinergic and might lead to a higher risk of adverse outcomes such as mortality. This study examined the risk of mortality in depressed elderly nursing home patients using paroxetine and other SSRIs. METHODS This study used 2007-2010 Minimum Data Set-linked Medicare data and a propensity score (PS)-matched retrospective cohort study design to achieve the study objective. New users of paroxetine and other SSRIs were followed until they reached the end of the follow-up period (1 year), switched to a different antidepressant class, used psychotherapy, or had a gap of more than 15 days in the use of index antidepressant class, whichever occurred earlier. A robust Cox proportional hazard (PH) model was used to evaluate the risk of mortality associated with the use of paroxetine and other SSRIs in depressed elderly nursing home residents. RESULTS The PS matching yielded 4620 patients each in the two treatment groups. The unadjusted incidence of mortality was 269 (2.9%) for paroxetine and 288 (3.1%) for other SSRIs users in the matched cohort. The robust Cox PH model did not find any significant difference in the risk mortality between the two groups (hazard ratio 1.01; 95% confidence interval 0.86-1.19). CONCLUSIONS This study did not find any significant difference in the risk of mortality between users of paroxetine and other SSRIs among elderly nursing home patients with depression. There is a need for further evaluation of other adverse effects of paroxetine due to its anticholinergic effects in the geriatric population.