Cigarette smoking is the leading cause of preventable death in the United States and produces substantial health-related economic costs to society. This report presents the annual estimates of the disease impact of smoking in the United States during 1995-1999. CDC calculated national estimates of annual smoking-attributable mortality (SAM), years of potential life lost (YPLL), smoking-attributable medical expenditures (SAEs) for adults and infants, and productivity costs for adults. Results show that during 1995-1999, smoking caused approximately 440,000 premature deaths in the United States annually and approximately $157 billion in annual health-related economic losses. Implementation of comprehensive tobacco-control programs as recommended by CDC could effectively reduce the prevalence, disease impact, and economic costs of smoking.