The Patient Health Questionnaire (PHQ-9) is a widely-used screening tool for depression in primary care settings. The purpose of the present study is to identify the factor structure of the PHQ-9 and to examine the measurement invariance of this instrument across different sociodemographic groups and over time in a sample of primary care patients in Spain. Data came from 836 primary care patients enrolled in a randomized controlled trial (PsicAP study) and a subsample of 218 patients who participated in a follow-up assessment at 3 months. Confirmatory factor analysis (CFA) was used to test one- and two-factor structures identified in previous studies. Analyses of multiple-group invariance were conducted to determine the extent to which the factor structure is comparable across various demo- graphic groups (i.e., gender, age, marital status, level of education, and employment situa- tion) and over time. Both one-factor and two-factor re-specified models met all the pre- established fit criteria. However, because the factors identified in the two-factor model were highly correlated (r = .86), the one-factor model was preferred for its parsimony. Multi-group CFA indicated measurement invariance across different demographic groups and across time. The present findings suggest that physicians in Spain can use the PHQ-9 to obtain a global score for depression severity in different demographic groups and to reliably monitor changes over time in the primary care setting.