This study assessed the safety and tolerability of sertindole in the long-term treatment of schizophrenia. An open-label, noncomparative, flexible-dose study was carried out in 11 European countries. Upon completion of an 8-week, haloperidol-referenced randomized clinical trial with sertindole, patients were offered sertindole maintenance treatment up to 18 months. In total, 294 patients were enrolled, of whom 237 (81%) had received sertindole and 57 (19%) had received haloperidol in the lead-in trial. The modal dose during the maintenance period was 16 mg/day. Patients showed therapeutic improvement indicated by significant decreases in the Positive And Negative Syndrome Scale and Clinical Global Impression ‘severity-of-illness’ scores. An adverse event was the primary reason for withdrawal in 13% of patients. The most common adverse events were fatigue and weight gain, both with incidences of 14%. The incidence of extrapyramidal symptoms was 18%, and 11% of the patients required anticholinergic medication. No statistically significant changes were observed in laboratory values or vital signs, but the mean serum prolactin levels decreased. The mean change in weight from baseline to the last assessment was 2.7 kg. The largest weight increase was observed in patients who were underweight at baseline. Long-term treatment with sertindole was safe and well tolerated, and patients showed clinical improvement beyond acute treatment.