OBJECTIVES: To examine the effects of initial ziprasidone dose on discontinuation rates, using PharMetrics integrated medical and pharmacy claims data. METHODS: Patients ≥ 18 years with a diagnosis of schizophrenia and a ziprasidone claim between March, 2001 and February, 2003, and continuously enrolled for ≥ 6 months before and ≥ 3 months after initiation of ziprasidone, were stratified by initial daily dose (≥ 40 to < 80 mg [Low] vs. ≥ 80 to < 120 mg [Medium] vs. 120–160 mg [High]). The 6-month risk of discontinuation was examined using Cox proportional hazards models controlling for gender, psychiatric comorbidities, and pre-ziprasidone utilization of antipsychotics (atypical, conventional, none). RESULTS: Mean age of the sample (N=1058) was 38 years; 42% were male. The 6-month risk of discontinuation was significantly greater in patients with a Low vs. a High initial dose (HR 0.74; 95% CI 0.58-0.94; P=0.012) and trended toward significance when comparing a Medium vs. a High initial dose (HR 0.86; 95% CI 0.69-1.10; P=NS). The largest difference in discontinuation rates between dose groups occurred after the first prescription. CONCLUSIONS: Patients initiating ziprasidone therapy with an initial dose of at least 120 mg/day demonstrated better medication adherence compared with those initiating at lower doses. This finding may reflect improved efficacy at daily doses ≥ 120 mg.