Objective: We estimated the reduction in number of hospitalizations for acute myocardial infarction and stroke as well as the associated health care costs resulting from reducing the number of smokers in the US federal workforce during a 5-year period. Methods: We developed a 5-year spreadsheet-based cohort model with parameter values from past literature and analysis of national survey data.We obtained 2015 data on the federal workforce population from the US Office of Personnel Management and data on smoking prevalence among federal workers from the 2013-2015 National Health Interview Survey. We adjusted medical costs and productivity losses for inflation to 2015 US dollars, and we updated future productivity losses for growth. Because of uncertainty about the achievable reduction in smoking prevalence and input values (eg, relative risk for acute myocardial infarction and stroke, medical costs, and absenteeism), we performed a Monte Carlo simulation and sensitivity analysis. Results: We estimated smoking prevalence in the federal workforce to be 13%. A 5 percentage-point reduction in smoking prevalence could result in 1106 fewer hospitalizations for acute myocardial infarction (range, 925-1293), 799 fewer hospitalizations for stroke (range, 530-1091), and 493 fewer deaths (range, 494-598) during a 5-year period. Similarly, estimated costs averted would be $59 million (range, $49-$63 million) for medical costs, $332 million (range, $173-$490 million) for absenteeism, and $117 million (range, $93-$142 million) for productivity. Conclusion: Reductions in the prevalence of smoking in the federal workforce could substantially reduce the number of hospitalizations for acute myocardial infarction and stroke, lower medical costs, and improve productivity. [ABSTRACT FROM AUTHOR]