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Objective: This study aimed to compare the incidence of dementia and all-cause mortality up to 20 years post-treatment in an index non-demented cohort between antipsychotic (AP) medication treatment and non-AP treatment groups., Methods: All patients in Kaiser Permanente Northern California with a major psychiatric diagnosis between 01/01/1996 and 12/31/2000, age ≥ 50 years, and without dementia diagnosis were included. The study cohort was divided into a "user group", patients treated with AP for ≥ 365 days (n = 1,829), and a "non-user group", propensity score-matched on age, sex, and race (n = 9,145). The association between AP exposure and dementia or mortality during the follow-up period (01/01/2001-12/31/2015) was evaluated using Cox proportional hazard models adjusted for psychiatric diagnosis, comorbidities, and other medications., Results: The user group had a hazard ratio (HR) of 2.2 (CI 1.8-2.7) for dementia and 1.3 (CI 1.2- 1.5) for death. The onset of dementia in the user group was significantly higher in patients aged ≤ 65 years (p < 0.001). The user group was sub-grouped into atypical, typical, and both; HR for dementia was 1.7 (CI 1.2-2.4), 2.5 (CI 1.9-3.1), and 1.8 (CI 1.4-2.4), respectively. Dementia and mortality were significantly higher in patients concurrently treated with benzodiazepine (HR 1.3; CI 1.2-1.5 and HR 1.4; CI 1.3-1.5) or tricyclic antidepressants (HR 1.2; CI 1.1-1.4 and HR 1.1; CI 1.0-1.2), respectively., Conclusion: Our preliminary results reveal an association between AP treatment and increased rates of both dementia and mortality. Future research is needed to substantiate our current findings., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)