OBJECTIVES: Treatment with antipsychotic medication is an important element of relapse prevention in the management of schizophrenia and can reduce inpatient stays. Recently, the long-acting atypical antipsychotic paliperidone long-acting injectable (PLAI), a once-monthly LAI antipsychotic, was approved for treatment of schizophrenia in Germany. The study aims at estimating, based on a previously published model, the cost-effectiveness of paliperidone long-acting injections compared to other common antipsychotic treatment strategies in patients diagnosed with schizophrenia in Germany. METHODS: A Markov decision analytic model was adapted to the German health care system. The model considers the cost-effectiveness for PLAI as a maintenance treatment for patients with schizophrenia from the payer perspective. The patients transition between eight health states on a monthly basis over a 5-year time horizon. As therapeutic strategies PLAI, quetiapine, risperidone long-acting injections (RLAI), oral olanzapine, oral risperidone, zuclopenthixol decanoate, olanzapine long-acting injections (OLAI), oral typical and oral atypical were compared. Probability of relapse, level of adherence, side effects and treatment discontinuation were derived from the Swedish original model. Input factors regarding resource use and costs were estimated and adjusted for the German health care system. A probabilistic sensitivity analyses using cost-effectiveness scatter plots was performed to visualize the robustness of the results. RESULTS: In base case scenario PLAI is superior to RLAI in gained quality adjusted life years (QALYs) and avoided relapses. Relative to all other treatment strategies PLAI is more effective with regard to gained QALYs and avoided relapses but results in higher treatment costs over a 5-year horizon in base case scenario. The results were tested in probabilistic sensitivity analyses CONCLUSIONS: PLAI dominates RLAI and compared to the other treatment strategies PLAI has shown to be more effective but results in higher costs in base case scenario.