Cultural and regional differences on the well-known elevated suicide risk in substance use disorders have not been clarified yet. Therefore, the suicide risk associated with substance use disorders in a society of transition and in a socially and economically stable society should be identified and compared. Data from two population-based matched case-control studies were used to analyse the association between alcohol and other substance consumption and the risk of suicide. Data in Frankfurt were obtained by a semi-structured interview including the Structured Clinical Interview for DSM-IV Axis I (SCID-I) in 163 suicides that occurred in 1999 and 2000, and data from Tallinn were collected according to DSM-IV criteria on 156 deceased persons who committed suicide in 1999 by using the psychological autopsy method and in each city in matched population-based control persons by personal interview. In both cities, substance use disorders were significantly associated with suicide. Odds ratios for suicide were higher in Tallinn than in Frankfurt. The highest risk was observed in Tallinn among men with alcohol use disorders, aged 35 to 59 years. Although substance use and, in particular, alcohol use disorders were confirmed as risk factors for suicide in Tallinn and in Frankfurt, the much higher suicide risk associated with alcoholism in Tallinn than in Frankfurt indicates the importance of cultural, socio-political, and regional impact of suicide risk in alcoholism.