This study aimed to validate and determine an appropriate cut-off score on the Thai Edinburgh Postnatal Depression Scale (EPDS) as a screen for postpartum depression. A prospective cohort of postpartum women at 6-8 weeks were tested using the EPDS and clinically interviewed by psychiatrists to establish a DSM-IV diagnosis of major or minor depressions in a university hospital in Southern Thailand. Of 351 postpartum women interviewed, 38 postpartum women met the criteria for depressive disorders, major depression in four women (1%) and minor depressive disorder in 34 women (10%). The area under the curve was 0.84 (95% confidence interval 0.76-0.91). Using an EPDS cut-off sum score of 6/7, major and/or minor depression was detected with a sensitivity of 74%, specificity of 74%, positive predictive value of 26% and negative predictive value of 95%. When the cut-off score was higher, the sensitivity was lower but the specificity was higher. The Thai version of the EPDS is a valid self-report instrument and is useful in Thailand where no other screening instrument for postpartum depression is available.