The present post-hoc analysis investigated the speed of onset of therapeutic effect of the atypical antipsychotic, risperidone, in direct comparison with conventional antipsychotics. Data were pooled from four double-blind active comparator-controlled clinical trials involving 757 patients with schizophrenia treated for up to 8 weeks with either risperidone (4–6 mg/day) or a conventional antipsychotic such as haloperidol (10 or 20 mg/day), perphenazine (mean dose 28 mg/day), or zuclopenthixol (mean dose 38 mg/day). Primary outcome was assessed using the Positive and Negative Syndrome Scale. A significantly greater proportion of patients treated with risperidone achieved ≥20% reduction from baseline Positive and Negative Syndrome Scale total score at weeks 1, 2, 6, and at end point (last observation carried forward: P≤0.04). A significant difference exists in mean reduction from baseline to end point in Positive and Negative Syndrome Scale total scores in favor of patients treated with risperidone compared with those treated with conventional antipsychotics (−18.4 vs −13.5; P=0.0013). The mean time to response was 23.8 days with risperidone and 28.2 days with conventional drugs (hazard ratio 1.3; 95% confidence interval 1.1–1.5). These findings are clinically relevant because the faster onset of therapeutic effect with atypical antipsychotics can be important in the acute setting and have a considerable impact on healthcare systems.