Background: Complications of influenza are a major cause of morbidity and mortality during the influenza season. Clinical trials of zanamivir have reported a reduced incidence of influenza complications among high-risk patients., Objectives: This retrospective study sought to determine whether the use of zanamivir lowers the risk of acute influenza complications in a broader population, based on an analysis of claims data from a large managed care organization., Methods: Medical and pharmacy health insurance claims data from October 1, 1999, through April 30, 2000, were compiled for UnitedHealthcare members in 19 states. All patients with a diagnosis of influenza (International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code 487.xx) associated with a physician visit were identified. From these, all patients were selected who had received zanamivir on the same day as the diagnosis of influenza. The propensity score matching technique was used to identify a comparison group with similar health service utilization and comorbidities who received a diagnosis of influenza but no antiviral therapy. Follow-up started the day after the influenza diagnosis and continued for 21 days., Results: From the 43,741 patients originally identified, 2341 were selected who received a simultaneous diagnosis of influenza and a prescription for zanamivir. The untreated comparator group numbered 2337. Fewer zanamivir patients than untreated patients were hospitalized for complications, and the absolute risks were low (0.6% and 1.0%, respectively; risk ratio [RR], 0.58; 95% CI, 0.30-1.12). Zanamivir-treated patients had an excess of outpatient visits (16.9% vs 14.5%; RR, 1.16; 95% CI, 1.02-1.33) and antibiotic use (16.3% vs 14.8%; RR, 1.10; 95% CI, 0.97-1.26), although the RRs were modest., Conclusions: In the setting of a large managed care plan, patterns of influenza complications were similar in zanamivir-treated and untreated patients with a diagnosis of influenza. The results of this study are in contrast to those of published clinical trials reporting a reduction in the risk of influenza complications in zanamivir-treated patients.