OBJECTIVES: Estimates of depression prevalence in pregnancy and postpartum are based on the Edinburgh Postnatal Depression Scale (EPDS) more than on any other method. We aimed to determine if any EPDS cutoff can accurately and consistently estimate depression prevalence in individual studies. METHODS: We analyzed datasets that compared EPDS scores to Structured Clinical Interview for DSM (SCID) major depression status. Random-effects meta-analysis was used to compare prevalence with EPDS cutoffs versus the SCID. RESULTS: Seven thousand three hundred and fifteen participants (1017 SCID major depression) from 29 primary studies were included. For EPDS cutoffs used to estimate prevalence in recent studies (>/=9 to >/=14), pooled prevalence estimates ranged from 27.8% (95% CI: 22.0%-34.5%) for EPDS >/= 9 to 9.0% (95% CI: 6.8%-11.9%) for EPDS >/= 14; pooled SCID major depression prevalence was 9.0% (95% CI: 6.5%-12.3%). EPDS >/=14 provided pooled prevalence closest to SCID-based prevalence but differed from SCID prevalence in individual studies by a mean absolute difference of 5.1% (95% prediction interval: -13.7%, 12.3%). CONCLUSION: EPDS >/=14 approximated SCID-based prevalence overall, but considerable heterogeneity in individual studies is a barrier to using it for prevalence estimation.