Objective Long‐acting injectable (LAI) antipsychotics were developed to improve adherence to schizophrenia treatment. Paliperidone palmitate (PP) has two LAI forms: Monthly (PP1M) and three‐monthly (PP3M). PP3M shows less difference in Peak‐to‐Trough drug concentration levels. This could be related to a lower incidence of hyperprolactinemia, which may negatively affect adherence. We aimed to compare prolactin levels and investigate relationships between prolactin levels, symptomatology and sexual function in patients with schizophrenia after switching from PP1M to PP3M. Methods Twenty‐five patients were enrolled. The sociodemographic data form, the Positive and Negative Syndromes Scale (PANSS) and the Arizona Sexual Experience Scale (ASEX) were used. Morning blood samples were drawn to determine prolactin levels. Results Prolactin level (p < 0.001), the total score and arousal sub‐score of ASEX (respectively; p = 0.015, p = 0.020) and the total score and positive scale of PANSS (respectively; p = 0.017, p = 0.021) were decreased on the 90th day (±15 days). Conclusions After switching to PP3M, the decreases in prolactin levels and potentially related sexual side effects was statistically significant. There may be a difference between two formulations of the same drug in terms of side effects, and there is a need for prospective follow‐up studies with larger samples.