Background and Objectives To determine the risk of hospitalization and death associated with pimavanserin use. Methods We conducted a retrospective cohort study of adults 65 years and older with Parkinson disease between November 1, 2015, and December 31, 2018, using an administrative dataset on residents of Medicare-certified long-term care facilities and linked Medicare claims data. Propensity score–based inverse probability of treatment weighting (IPTW) was used to balance pimavanserin users and nonusers on 24 baseline characteristics. Fine-Gray competing risk and Cox proportional hazards regression models were used to estimate the risk of hospitalization and death up to 1 year, respectively. Results The study cohort included 2,186 pimavanserin users and 18,212 nonusers. There was a higher risk of 30-day hospitalization with pimavanserin use vs nonuse (IPTW-adjusted hazard ratio [aHR] 1.24, 95% confidence intervals [CI] 1.06–1.43). There was no association of pimavanserin use with 90-day hospitalization (aHR 1.10, CI 0.99–1.24) or with 30-day mortality (aHR 0.76, CI 0.56–1.03). Pimavanserin use vs nonuse was associated with increased 90-day mortality (aHR 1.20, CI 1.02–1.41) that persisted after 180 days (aHR 1.28, CI 1.13–1.45) and 1 year (aHR 1.56, CI 1.42–1.72). Discussion Pimavanserin use vs nonuse in older adults was associated with an increased risk of hospitalization at 1 month of initiation and a higher risk of death for up to 1 year following initiation. These findings, in a large real-world cohort within long-term care facilities, may help to inform decisions regarding its risk/benefit balance among patients with Parkinson disease. Classification of Evidence This study provides Class II evidence that in patients with Parkinson disease who are 65 or older and residing in Medicare-certified long-term care facilities, pimavanserin is associated with an increased risk of 30-day hospitalization and higher 90-, 180-, and 365-day mortality.