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To find a best-fitting factor structure of the Center for Epidemiological Studies Depression (CES-D) and test whether this structure is invariant across gender in a cardiac rehabilitation population.We examined the data from 920 participants of a cardiac rehabilitation exercise program. Fourteen confirmatory factor analyses were conducted to examine existing factor solutions from the literature. The best-fitting model was tested for invariance across gender.The data fit best to a 3-factor solution, which has 14 items and 3 factors (ie, somatic symptoms, negative affect, and anhedonia). The goodness-of-fit indices showed an acceptable fit. The invariance analysis revealed that the factor structure is equivalent across gender.While a fitting factor solution was found, rehabilitation practitioners and researchers need to be aware of the psychometrical shortcomings of the CES-D and consider using other scales as alternative measures of depressive symptoms.