OBJECTIVE : The aim was to compare adherence to antipsychotics (APs), healthcare resource utilization (HRU), and costs before and after once-every-3-months paliperidone palmitate (PP3M) initiation in patients with schizophrenia. METHODS : Medicaid data (Iowa, Kansas, and Missouri; 1/2014-3/2017) were used to identify adults with at least one PP3M claim, ≥ 12 months of pre-index enrollment, and at least two schizophrenia diagnoses. Adequate treatment with once-monthly paliperidone palmitate (PP1M) was required pre-PP3M transition. Generalized estimating equations were used to assess linear trends in adherence to APs, HRU, and costs over the four quarters pre-PP3M transition, and to compare monthly HRU and costs 6 months pre- and 12 months post-PP3M transition as well as adherence to APs 12 months pre- and post-PP3M transition. RESULTS : Among 324 patients initiated on PP3M, the mean age was 41.4 years and 36.1% were females. Over the four quarters pre-PP3M transition, the monthly number of emergency room visits, medical costs, and inpatient costs decreased, while pharmacy costs and adherence to APs increased. For patients with ≥ 12 months of follow-up (n = 151), adherence to APs (66.2 vs. 70.2%, p = 0.3758), total (US$3371 vs. US$3456; p = 0.7000), pharmacy (US$1805 vs. US$1870; p = 0.2960), and medical costs (US$1565 vs. US$1586; p = 0.9040) remained similar pre- and post-PP3M transition, while mean monthly number of 1-day mental institute visits (1.71 vs. 1.51; p < 0.01) and associated costs (US$260 vs. US$232, p = 0.01) decreased. CONCLUSIONS : Adherence to APs, HRU, and costs were similar pre- and post-PP3M transition, suggesting that PP3M has no impact on monthly costs for patients adequately treated with PP1M, with the added flexibility of once-every-3-months dosing.