Background: The purpose of the present nationwide psychological autopsy case-control study is to identify the association between mental disorders and suicide in Japan, adjusting for physical conditions. Methods: A semi-structured interview was conducted of the closest family members of 49 suicide completers and 145 gender-, age-, and municipality-matched living controls. The interview included sections of socio-demographic characteristics, physical conditions, and a psychiatric interview producing DSM-IV diagnoses of mental disorders prior to suicide (or at survey). We compared prevalences of mental disorders between the two groups, using conditional logistic regression. Results: A significantly higher proportion with any mental disorder was found in the suicide group (65.3%) compared to the control group (4.8%) (p = 0.003, odds ratio [OR] = 7.5). The population attributable risk proportion associated with mental disorder was 0.24. Mood disorder, particularly major depressive disorder, was the most strongly associated with suicide (p < 0.001). Anxiety disorder, alcohol-related disorder, and brief psychotic disorder were also significantly associated with suicide (p < 0.05). These patterns were unchanged after adjusting for serious chronic physical conditions. Limitations: The present study had some limitations, such as small sample size, sampling bias and information bias. Conclusions: Most mental disorders, particularly mood disorder, were significantly associated with a greater risk of suicide in Japan, independent of physical conditions. Mental disorders are a major target of suicide prevention programs in Japan. © 2012 Elsevier B.V.