AbstractEven today, patients with schizophrenia often have an unfavorable outcome. Negative symptoms and cognitive deficits are common features in many patients and prevent recovery. In recent years, aerobic endurance training has emerged as a therapeutic approach with positive effects on several domains of patients’ health. However, appropriately sized, multicenter randomized controlled trials that would allow better generalization of results are lacking. The exercise study presented here is a multicenter, rater-blind, two-armed, parallel-group randomized clinical trial in patients with clinically stable schizophrenia being conducted at five German tertiary hospitals. The intervention group performs aerobic endurance training on bicycle ergometers three times per week for 40–50 min/session (depending on the intervention week) for a total of 26 weeks, and the control group performs balance and tone training for the same amount of time. Participants are subsequently followed up for 26 weeks. The primary endpoint is all-cause discontinuation; secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and explorative biological measures regarding the underlying mechanisms of exercise. A total of 180 patients will be randomized. With currently 162 randomized participants, our study is the largest trial to date to investigate endurance training in patients with schizophrenia. We hypothesize that aerobic endurance training has beneficial effects on patients’ mental and physical health, leading to lower treatment discontinuation rates and improving disease outcomes. The study results will provide a basis for recommending exercise interventions as an add-on therapy in patients with schizophrenia.The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).