Even though the strong association between physical inactivity and ill health is well documented, 60% of the population is inadequately active or completely inactive. Traditional methods of prescribing exercise have not proven effective for increasing and maintaining a program of regular physical activity. To compare the 24-month intervention effects of a lifestyle physical activity program with traditional structured exercise on improving physical activity, cardiorespiratory fitness, and cardiovascular disease risk factors. Randomized clinical trial conducted from August 1, 1993, through July 31, 1997. Sedentary men (n = 116) and women (n = 119) with self-reported physical activity of less than 36 and 34 kcal/kg per day, respectively. Six months of intensive and 18 months of maintenance intervention on either a lifestyle physical activity or a traditional structured exercise program. Primary outcomes were physical activity assessed by the 7-Day Physical Activity Recall and peak oxygen consumption (VO2peak) by a maximal exercise treadmill test. Secondary outcomes were plasma lipid and lipoprotein cholesterol concentrations, blood pressure, and body composition. All measures were obtained at baseline and at 6 and 24 months. Both the lifestyle and structured activity groups had significant and comparable improvements in physical activity and cardiorespiratory fitness from baseline to 24 months. Adjusted mean changes (95% confidence intervals [CIs]) were 0.84 (95% CI, 0.42-1.25 kcal/kg per day; P<.001) and 0.69 (95% CI, 0.25-1.12 kcal/kg day; P = .002) for activity, and 0.77 (95% CI, 0.18-1.36 mL/kg per minute; P = .01) and 1.34 (95% CI, 0.72-1.96 mL/kg per minute; P<.001) for VO2peak for the lifestyle and structured activity groups, respectively. There were significant and comparable reductions in systolic blood pressure (-3.63 [95% CI, -5.54 to -1.72 mm Hg; P<.001] and -3.26 [95% CI, -5.26 to -1.25 mm Hg; P = .002]) and diastolic blood pressure (-5.38 [95% CI, -6.90 to -3.86 mm Hg; P<.001] and -5.14 [95% CI, -6.73 to -3.54 mm Hg; P<.001) for the lifestyle and structured activity groups, respectively. Neither group significantly changed their weight (-0.05 [95% CI, -1.05 to 0.96 kg; P = .93] and 0.69 [95% CI, -0.37 to 1.74 kg; P = .20]), but each group significantly reduced their percentage of body fat (-2.39% [95% CI, -2.92% to -1.85%; P<.001] and -1.85% [95% CI, -2.41 % to -1.28%; P<.001]) in the lifestyle and structured activity groups, respectively. In previously sedentary healthy adults, a lifestyle physical activity intervention is as effective as a structured exercise program in improving physical activity, cardiorespiratory fitness, and blood pressure.