Designed to provide information about patients with schizophrenia who switch from depot neuroleptics to the oral, atypical antipsychotic risperidone, this multicenter observational study enrolled patients who wished to stop the depot, had an unsatisfactory response, or experienced unacceptable side effects. Individuals remained on depot medication for 4 weeks and then received risperidone monotherapy for 3 months. Of the 143 patients who entered the study, 130 received risperidone, 109 completed the initial 16-week study, and 88 entered an optional 12-week follow-up. Symptoms and side effects did not change significantly during the depot phase (mean Positive and Negative Syndrome Scale [PANSS] score 72.2 at baseline, 71.6 at visit 2), but PANSS scores, global assessment of functioning, parkinsonism, and dyskinesia improved significantly during the risperidone phase (mean PANSS score decreased from 71.6 to 55.5 after 3 months). The number of contacts with healthcare professionals fell significantly during the risperidone phase; in addition, symptomatic improvements were maintained during follow-up, and movement disorders continued to decrease significantly. The investigators considered that 81% of patients had switched successfully. Patient acceptance of risperidone was significantly higher than for depot medication (83% vs 23%; P<.001), and 65% considered risperidone better than their previous treatment. Indications for depot medication should be reviewed, and patients may benefit from a switch to risperidone.