BACKGROUND: Concern about underdiagnosis and undertreatment of depression in primary care has led to support for routine screening. Although multiple screening instruments exist, we are not aware of studies to date that have compared different screening strategies, e.g., how the instrument is administered: by whom and in what setting. This study compared 3 separate screening strategies in terms of patient flow, coverage, patient characteristics, and other factors with the usual care system of provider referral. METHOD: We analyzed existing data from a completed randomized team trial of collaborative care depression treatment in which patients who met DSM-IV criteria for current major depressive disorder, dysthymic disorder, or both were recruited using the usual care system of provider referral (provider) and 3 separate screening strategies: (1) a 2-stage waiting room screening interview (waiting), (2) an in-clinic screen consisting of 2 self-report items embedded in a larger survey (in-clinic), and (3) a 2-stage self-report mail survey (mail). The team trial and analysis were conducted between January 1998 and July 2003. RESULTS: The usual care system of provider referral identified the most depressed patients and had relatively good coverage compared with the 3 screening strategies. Of the 3 screening strategies, the in-clinic strategy had the best coverage, while the mail strategy had the worst coverage. Provider referral patients were younger and had fewer chronic medical illnesses than did other patients. The waiting strategy identified more patients with bipolar affective disorder. CONCLUSION: While different strategies may be optimal for different resource levels and patient characteristics, this study suggests that an in-clinic self-report survey may be the best adjunct to provider referral for efficiently increasing coverage. This study also suggests that different screening strategies may capture different patient populations.