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Context: A growing body of reports has documented the ability of anticoagulation management services to help patients receiving warfarin therapy achieve better outcomes compared to the care provided by their personal physicians (ie, usual care)., Objective: To compare clinical outcomes associated with anticoagulation therapy provided by a clinical pharmacy anticoagulation service (CPAS) to usual care., Design: Retrospective, observational cohort study, 6 months in duration., Setting: Large nonprofit, group-model health maintenance organization., Patients: A total of 6,645 patients receiving warfarin therapy were included in the final analyses (intervention group, 3,323 patients; control group, 3,322 patients)., Intervention: Anticoagulation therapy for patients in the intervention group was managed by a centralized, telephonic CPAS. Therapy for patients in the control group was managed in the usual manner by their personal physicians., Main Outcome Measures: The primary outcome was the occurrence of anticoagulation therapy-related complications. A secondary outcome was the proportion of time spent in the target international normalized ratio (INR) range for each patient. Cox proportional hazards regression analyses were used to examine the risk of complications in relation to the study group., Results: Patients in the CPAS were 39% less likely to experience an anticoagulation therapy-related complication than were patients in the control group (hazard ratio, 0.61; 95% confidence interval, 0.42 to 0.88). The number of patients needed to treat to prevent an anticoagulation therapy complication was 52. Additional analyses revealed that improved outcomes associated with CPAS were mediated largely through improved therapeutic INR control. Patients in the CPAS group spent 63.5% of study period days within their target INR range compared to 55.2% in the control group (p < 0.001)., Conclusions: A centralized, telephonic, pharmacist-managed anticoagulation monitoring service reduced the risk of anticoagulation therapy-related complications compared to that with usual care. The cumulative evidence supporting the superior care associated with implementing a pharmacist-managed anticoagulation monitoring service was sufficient to recommend widespread implementation.