BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) is widely used in many countries to screen women for depression in the perinatal period. However, across studies the psychometric properties and cutoff scores of the EPDS have varied considerably; potentially due to different depression criteria and diagnostic systems being used. Therefore, we validated the Danish EPDS against a depression diagnosis according to both DSM-5 and ICD-10. Furthermore, we examined whether the Danish EPDS is multidimensional, as it has previously been suggested. METHODS: Women (N = 324) were recruited after routine screenings with the EPDS between 2 and 10 months postpartum (T1). At a subsequent home visit (T2), the EPDS and the Structured Clinical Interview for DSM-5 were administered. Diagnostic interviews were audio recorded to enable subsequent coding for ICD-10 diagnoses and inter-rater reliability analysis. A two-phase stratified sampling strategy with three sampling categories (EPDS-score at T1) was used. Using the distribution of 4931 T1 EPDS-scores from the same population from which we sampled the participants, we used sampling weighing to reweight the sample. The calculation of weights was based upon the mother's sampling category at T1 (i.e. the probability of being sampled) and the weights were applied when assessing the receiver operation characteristics (ROCs) of the EPDS. Sensitivity, specificity, positive predictive value, negative predictive value and area under the ROC curve were computed from the reweighted data for all relevant cutoff values. CIs were computed by embedding the calculations in a weighted logistic regression. Exploratory factor analysis was done using oblique rotation. Parallel analysis was used to assess the number of factors. RESULTS: A score of 11 or more was found to be the optimal cutoff for depression according to both DSM-5 and ICD-10 criteria. Factor analysis suggested that the Danish EPDS consists of three factors, including an 'anxiety factor'. CONCLUSIONS: The Danish EPDS has reasonable sensitivity and specificity at a cutoff score of 11 or more. There are no notable differences with respect to using ICD-10 or DSM-5 criteria for depression in terms of optimal cutoff. The variation in cutoff scores is likely to be due to cultural variations in the expression of depressive symptoms.