Measures of quality of life have been increasingly used in clinical trials. When designing a study, researchers must decide which quality of life measure to use. Some literature provides guidance through general recommendations, though lacks quantitative comparisons. In this report, 2 general quality of life measures, the 12-Item Short Form Health Survey (SF-12) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), are compared in a depressed population. STAR*D data were used to analyze the associations among the SF-12 and the Q-LES-Q. Each measure covers 6 domains, overlapping on 5 (health, self-esteem/well-being, community/productivity, social/love relationships, leisure/creativity), with the SF-12 addressing family and the Q-LES-Q addressing living situations. Strong item-by-item associations exist only between the Q-LES-Q and the SF-12 physical health items. The 2 measures overlap on the domains covered while the lack of correlation between the 2 measures may be attributed to the perspective of each question as the Q-LES-Q measures satisfaction while the SF-12 measures the patient's perception of function. © 2007 Lippincott Williams & Wilkins, Inc.