Clozapine has shown consistent efficacy against positive symptoms of psychoses, and emerging reports indicate improvements in aggression and suicidality. This study evaluated the impact of clozapine aggression in a psychiatric hospital. Over a three year period, 137 subjects with schizophrenia or schizoaffective disorder received clozapine, of whom nearly 50% (n=69) experienced seclusion or restraint. Using a mirror-image study design, seclusion and restraint rates were computed per patient-month pre-clozapine and compared during clozapine treatment to a maximum of 12 months in either direction. The rest of the hospital not receiving clozapine served as a comparator group. Statistically significant reductions occurred in both seclusion (0.44+/-0.46 vs. 0.16+/-0.32, z=-3.91, p=0.0003) and restraint (0.34+/-0.47 vs. 0.08+/-0.23, z=-2.27, p=0.032) during clozapine treatment as compared with the pre-clozapine period. The comparator group experienced a low rate of seclusion and restraint throughout. While there are limitations to a mirror-image design, this study supports the emerging data on the benefits of clozapine for aggressive and violent patients with psychoses. Preliminary data suggests other second generation antipsychotic agents may have similar effects.