BACKGROUND: High salt intake is a major modifiable risk factor of hypertension which is prevalent in India. It is not yet clear if salt substitutes reduce blood pressure (BP) among Indian hypertensive patients. OBJECTIVES: Examine the acceptability, usage, and BP effects of a reduced-sodium and added-potassium salt substitute among hypertensive patients. METHODS: We enrolled 502 participants with hypertension (aged 61.6 ± 12.0 y, 58.8% women) from 7 villages in rural India. Participants were randomly assigned to receive either regular salt (100% sodium chloride) or the salt substitute (70% sodium chloride/30% potassium chloride blend), and advised to replace all home salt use. The primary outcome was the change in systolic BP (SBP) from baseline to 3 mo comparing the salt substitute and regular salt groups. Secondary outcomes included the change in diastolic BP (DBP), 24-h urinary biomarkers, and self-reported use and satisfaction with the study salt provided. RESULTS: A total of 494 (98%) participants completed 1 mo and 476 (95%) participants completed the 3-mo follow-up. At 3 mo, the salt substitute intervention significantly decreased the average SBP by 4.6 mmHg (95% CI: 3.0, 6.2, P < 0.001) and DBP by 1.1 mmHg (95% CI: 0.2, 2.1 mmHg, P = 0.02). There was a significant increase in 24-h urinary potassium excretion in the salt substitute group by 0.24 g/d (95% CI: 0.12, 0.35 g/d, P < 0.001) and a decrease in the urinary sodium to potassium ratio by 0.71 (95% CI: 0.55, 0.87, P < 0.0001) compared with the control group. Participants reported that they used the study salt nearly every day of the week (mean ± SD, 6.3 ± 1.8 d) and rated the taste of the study salts similarly. CONCLUSION: The reduced-sodium added-potassium salt led to a substantial reduction in SBP in hypertensive patients, supporting salt substitution as an effective, low-cost intervention for BP lowering in rural India. This trial was registered at clinicaltrials.gov as NCT03909659.