OBJECTIVE: People infected with the human immunodeficiency virus are at an increased risk of developing ischemic heart disease (IHD); however, the effects of an education and home-based pedometer walking program on risk factors of IHD are not known. METHODS: We conducted a 12-month randomized study of an education and home-based pedometer walking program in 84 human immunodeficiency virus-infected individuals with risk factors of IHD. RESULTS: Pedometer step count of the control and intervention groups improved significantly (P = 0.03 for both groups) at 6 months but was not significant at 12 months (P = 0.33 and 0.21, respectively). Significant between-group effects were observed in 6-minute walk test distance (P = 0.01), waist to hip ratio (P = 0.00), glucose (P = 0.00), and high-density lipoprotein (P = 0.01) over the 12-month period. The program did not result in change in high-sensitivity C-reactive protein as it was associated with perceived stress (r = 0.23; P = 0.03), weight (r = 0.28; P = 0.01), body mass index (r = 0.35; P < 0.00), waist (r = 0.28; P = 0.01) and hip circumference (r = 0.28; P = 0.01). Multivariate generalized estimation equation analysis demonstrated an inverse association between interaction and perceived stress (logB = -0.01; 95% confidence interval: -0.02 to -0.01; P <0.00) and body mass index (logB = -0.02; 95% confidence interval: -0.03 to -0.002; P = 0.02) at group level. CONCLUSION: An education and home-based pedometer walking program improves physical activity levels, and beneficial changes in other IHD risk factors were noted.