The Montgomery–Åsberg Depression Rating Scale (MADRS) is a widely used clinician-rated measure of depressive severity. Empirical support for the factor structure of the MADRS is mixed; further, the comparison of MADRS scores within and between patients requires the demonstration of consistent instrument properties. The objective of the current investigation was to evaluate MADRS factor structure as well as MADRS factorial invariance across time and gender. The MADRS was administered to 821 depressed outpatients participating in a large-scale effectiveness study of combined pharmacotherapy and psychotherapy for depression. Treatment outcome did not differ across treatment groups. Factor structure and invariance was evaluated via confirmatory factor analysis. A four-factor model consisting of Sadness, Negative Thoughts, Detachment and Neurovegetative symptoms demonstrated a good fit to the data. This four-factor structure was invariant across time and gender. A hierarchical model, in which these four factors served as indicators of a general depression factor, was also supported. A limitation of the current study is the lack of comprehensive characterization of patient clinical features; results need to be replicated in more severely depressed or treatment refractory patients. Overall, evidence supported the use of the MADRS total score as well as subscales focused on affective, cognitive, social and somatic aspects of depression in male and female outpatients. Copyright © 2013 John Wiley & Sons, Ltd.