Background: The nationally reported Healthcare Effectiveness Data and Information Set (HEDIS) antidepressant medication management measure assesses whether patients with new episodes of depression receive antidepressant coverage for 84 of the first 114 days of treatment. Although initial prescriptions for a 90-day supply satisfy measure requirements, they may circumvent its purpose of ensuring adequate medication management. Objectives: To assess the extent to which 90-day initial prescriptions have contributed to health system performance on the HEDIS antidepressant measure from fiscal years 2001 to 2008. Research Design: Retrospective cohort analysis of Veterans Health Administration administrative data. Subjects: Patients with a new diagnosis of depression and a new antidepressant prescription (N = 383,634). Measures: HEDIS antidepressant measures, days supply of initial antidepressant prescriptions, antidepressant refills, and clinical encounters. Results: Health system performance on the HEDIS acute phase antidepressant measure increased from 63.1% in 2001 to 71.0% in 2008. Receipt of an initial 90-day antidepressant supply increased from 10.5% to 29.1% during this same period; when these are excluded, HEDIS performance was 58.8% in 2001 and 59.4% in 2008. Receiving an initial 90-day prescription was associated with prior antidepressant treatment, fewer clinical encounters, and similar rates of antidepressant refills compared with patients prescribed less than 90-day supplies. Conclusion: Although increases in initial 90-day supplies contribute to improved performance on the HEDIS measure, actual adherence during the acute treatment phase may not be changed by this practice. Quality measures based on pharmacy fills may need modification in the setting of large initial prescriptions.