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This study was designed to assess trends in cigarette, illicit drug, and heavy alcohol use among active-duty military personnel from 1980 to 2005 and to examine the influence of socio-demographic changes within the military on patterns of substance use.Substance use prevalence rates were estimated from cross-sectional data obtained from nine self-report surveys administered to more than 150 000 active-duty service members world-wide over a 25-year period. Direct standardization was used to adjust for socio-demographic changes.Measures included self-reported cigarette use, illicit drug use and heavy alcohol use in the 30 days prior to the survey. Heavy alcohol use was defined as drinking five or more drinks per typical drinking occasion at least once a week in the past 30 days.Cigarette and illicit drug use among military personnel declined sharply and significantly from 1980 to 1998. Heavy alcohol use decreased in the mid-1980s but was stable from 1988 to 1998. Both cigarette smoking and heavy alcohol use increased significantly between 1998 and 2002 and remained at those levels in 2005. Illicit drug use remained low. Logistic regression analyses indicated that trends were influenced by other factors besides socio-demographic changes across survey years.The military has made notable progress in decreasing cigarette smoking and illicit drug use, but has made less progress in reducing heavy alcohol use. Additional emphasis should be placed on understanding recent increases in substance use and on planning effective interventions and prevention programs to reduce use in this high-risk population.