It was reported that ritanserin, a 5HT2A/2C antagonist, improves negative symptoms when added to neuroleptics in inpatients with predominantly negative symptoms. Nevertheless, the results of published studies are contradictory so far. This study was designed to investigate the effect of ritanserin added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double blind and randomized clinical trial. Eligible participants in this study were 40 patients with chronic schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion, 20 to risperidone 6 mg/day plus ritanserin 12 mg/day (6 mg bid) and 20 to risperidone 6 mg/day plus placebo. The principal measure of the outcome was Positive and Negative Syndrome Scale (PANSS). Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of risperidone and ritanserin showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores. The present study indicates ritanserin as a potential adjunctive treatment strategy for the negative symptoms of schizophrenia. Nevertheless, results of larger controlled trials are needed, before recommendation for a broad clinical application can be made.