Background: Eighty percent of premature mortality from cardiovascular disease occurs in low- and middle-income countries. Hypertension, diabetes, and smoking are the top risk factors causing this disease burden. Objectives: The study aimed to test the hypothesis that utilizing community health workers (CHWs) to manage hypertension, diabetes and smoking in an integrated manner would lead to improved control of these conditions. Methods: This was a 2-year cluster (n = 12) randomized controlled trial of 3,556 adults (35 to 70 years of age) in a single town in India, who were screened at home for hypertension, diabetes, and smoking. Of these adults, 1,242 (35%) had at least 1 risk factor (hypertension = 650, diabetes = 317, smoking = 500) and were enrolled in the study. The intervention group had behavioral change communication through regular home visits from community health workers. The control group received usual care in the community. The primary outcomes were changes in systolic blood pressure, fasting blood glucose, and average number of cigarettes/bidis smoked daily among individuals with respective risk factors. Results: The mean ± SD change in systolic blood pressure at 2 years was −12.2 ± 19.5 mm Hg in the intervention group as compared with −6.4 ± 26.1 mm Hg in the control group, resulting in an adjusted difference of –8.9 mm Hg (95% confidence interval [CI]: –3.5 to –14.4 mm Hg; p = 0.001). The change in fasting blood glucose was −43.0 ± 83.5 mg/dl in the intervention group and −16.3 ± 77.2 mg/dl in the control group, leading to an adjusted difference of –21.3 mg/dl (95% CI: 18.4 to –61 mg/dl; p = 0.29). The change in mean number of cigarettes/bidis smoked was nonsignificant at +0.2 cigarettes/bidis (95% CI: 5.6 to –5.2 cigarettes/bidis; p = 0.93). Conclusions: A population-based strategy of integrated risk factor management through community health workers led to improved systolic blood pressure in hypertension, an inconclusive effect on fasting blood glucose in diabetes, and no demonstrable effect on smoking. (Study of a Community-Based Approach to Control Cardiovascular Risk Factors in India [SEHAT]; NCT02115711).