Subjects who completed a randomized, double-blind, 18-week, trial comparing clozapine and ziprasidone in refractory or treatment-intolerant schizophrenic patients and who responded to treatment with ziprasidone (≥ 20% reduction in PANSS total score) were enrolled in a 1-year, open-label, flexible-dose study. Subjects received the same dose of ziprasidone (80-160 mg/day) upon which they completed the double-blind study. Dose changes were permitted based on clinical impression of efficacy or adverse events. The change in PANSS total score from baseline to endpoint and the proportion of patients maintaining ≥ 20% PANSS improvement at endpoint were recorded. Safety measures included adverse events, laboratory tests, body weight, vital signs, and electrocardiograms. Of 45 patients who completed the initial study, 42 were enrolled in the study and 40 were included in the intent-to-treat analysis. The mean change from core study baseline in PANSS total score was –37.0 (95% CI, –41.8 to –2.2; P < 0.001) on entry to the extension study. Following 1 year of oral ziprasidone, the mean change in PANSS total score from core study baseline was –32.2 (95% CI, –39.1 to –25.3; P < 0.001), a change from extension study baseline of 5.1 ± 16.7 (P = 0.061). Of the 40 patients, 28 (70%) maintained ≥ 20% reduction in PANSS total score (vs core study baseline) at the extension study endpoint. The safety evaluation showed no detrimental effects. These findings show that the efficacy and safety of ziprasidone observed in refractory or treatment-intolerant schizophrenic patients are maintained in a long follow-up period.