To evaluate the validity and reliability of the structured Composite International Diagnostic Interview (CIDI) in diagnosing current major depressive disorder (MDD) among East African adults. A sample of 926 patients attending a major referral hospital in Ethiopia participated in this diagnostic assessment study. We used a two-stage study design where participants were first interviewed using an Amharic version of the CIDI and a stratified random sample underwent a follow-up semi-structured clinical interview conducted by a psychiatrist, blinded to the screening results, using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) instrument. We tested construct validity by examining the association of the CIDI and World Health Organization Quality of Life (WHO-QOL) questionnaire. We calculated the psychometric properties of the CIDI using the SCAN diagnostic interview as a gold standard. We found that the Amharic version of the CIDI diagnostic interview has good internal reliability (Cronbach's alpha = 0.97) among Ethiopian adults. Compared to the SCAN reference standard, the CIDI had fair specificity (72.2%) but low sensitivity (51.0%). Our study provided evidence for unidimensionality of core depression screening questions on the CIDI interview with good factor loadings on a major core depressive factor. The Amharic language version of the CIDI had fair specificity and low sensitivity in detecting MDD compared with psychiatrist administered SCAN diagnosis. Our findings are generally consistent with prior studies. Use of fully structured interviews such as the CIDI for MDD diagnosis in clinical settings might lead to under-detection of DSM-IV MDD.