The Multiple Risk Factor Intervention Trial (MRFIT) is a 6-year clinical trial for the study of the prevention of heart disease. Twelve thousand eight hundred and sixty-six men in the upper 10–15% of heart attack risk were randomly assigned to Special Intervention (SI) or Usual Care (UC). The SI participants received “risk factor” (hypertension, hypercholesterolemia, and cigarette smoking) intervention at the clinical centers; the UC participants were referred to their usual source of medical care for treatment. Forty percent of SI and 21% of UC smokers at entry reported not smoking at year 4, with lighter smokers in both treatment groups reporting significantly more cessation than heavier smokers. The greatest SI-UC difference in cessation rate was achieved during the first year of the program. The use of serum thiocyanate, an objective indicator of cigarette smoking, avoided problems inherent in self-reported data. Misreporting of smoking status was found in both groups with more occurring among the SI smokers. Cohort analysis revealed that of the smokers who stopped during the first year of the trial, 68% of SI and 57% of UC remained abstinent through the 4-year follow-up. Of the smokers who stopped later in the program the UC had better maintenance rates than the SI.