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Our aim was to determine the effect of risperidone monotherapy treatment on disability and on the quality of life of 318 schizophrenic outpatients who had been previously treated with other neuroleptics. Patients were assessed at baseline 2, 4 and 8 months using the BPRS, CGI, WHO/DDS and SF-36. BPRS scores showed a significant decrease at month 2, both in the total score and in each of the three clusters, negative, positive and depression/anxiety. WHO/DDS scores significantly decreased both in the overall score (from 51.8 to 37.4, P < 0.0001) and in the four dimensions. SF-36 scale scores and summary measures showed a significant improvement after 8 months of risperidone treatment. Risperidone long-term treatment (8 months) has a positive effect on clinical and on psychosocial outcomes. Females, paranoids patients and patients without history of use-abuse of substances showed greater improvements in quality of life.