Risperidone ISM® (OKEDI®), a new long-acting formulation of the atypical antipsychotic risperidone manufactured using in situ microparticle technology, has been available in Germany since April 2022, in Austria since February 2023. Effective plasma levels are achieved as early as 2 hours after IM injection without loading dose or oral supplementation with risperidone. The results of the phase III PRISMA-3 study (n = 438) show that therapy with risperidone ISM® is associated with a significant reduction in severe to moderate psychotic symptoms (mean positive and negative syndrome scale [PANSS] total score) as well as in Clinical Global Impression Improvement (CGI-I) scores with a high effect size (p < 0.0001). The difference from placebo in PANSS total score, positive syndrome score, and overall response reached statistical significance from day 8 (100-mg dose) and day 15 (75 mg), respectively. Adverse events were mostly mild (67.8 %) or moderate (28.0 %) and comparable to those seen with oral risperidone. In the open-label extension study, patients who had completed the phase III study patients pre-treated either with risperidone ISM® or placebo (n = 174) received risperidone ISM® for 12 months. In addition, a group of patients was treated with risperidone ISM® 75 mg or 100 mg de novo (n = 41). Thereby, the mean PANSS total score improved in all treatment groups to the endpoint, most significantly in placebo or risperidone ISM® pre-treated patients. Thus, the new atypical depot antipsychotic risperidone ISM® is suitable for early treatment of patients subsequent to acute phase schizophrenia as well as for maintenance therapy and relapse prophylaxis. The prerequisite for use is that the efficacy and tolerability of risperidone or paliperidone are known; if necessary, individual oral tolerability should be tested prior to administration of risperidone ISM®. Patients may particularly benefit from risperidone ISM® who have had problems in the past with the up-dosing of antipsychotic treatment as well as patients with adherence issues.