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Because of the high patient load in Thailand, we need a practical measurement to help primary physicians detect depression. This study aimed to examine the reliability and validity of the Thai version of the World Health Organization-Five Well-Being Index (WHO-5-T), which is short and easy to use as a screening tool for major depression in primary care patients.The English version of the WHO-Five Well-Being Index was translated into Thai. Back-translations, cross-cultural adaptation and field testing of the pre-final version with final adjustments were performed accordingly. The WHO-5-T was administered randomly to 300 patients in our primary care clinic. Then the patients were further assessed using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression as the gold standard of diagnosis and symptom severity, respectively.Completed data were obtained from 274 respondents. Their mean age was 44.6 years [standard deviation (SD) = 14.7] and 73.7% of them were female. The mean WHO-5-T score was 14.32 (SD = 5.26). The WHO-5-T had a satisfactory internal consistency (Cronbach's alpha = 0.87) and showed moderate convergent validity with the Hamilton Rating Scale for Depression (r = −0.54; P < 0.001). The optimal cut-off score of the WHO-5-T <12 revealed a sensitivity of 0.89 and a specificity of 0.71 in detecting depression. The area under the curve in this study was 0.86 (SD = 0.03, 95% confidence interval 0.81 to 0.89).The Thai version of the WHO-Five Well-Being Index was found to be a reliable and valid self-assessment to screen for major depression in primary care setting at a cut-off point of <12.