Background: SSaSS (Salt Substitute and Stroke Study), a 5-year cluster randomized controlled trial, demonstrated that replacing regular salt with a reduced-sodium, added-potassium salt substitute reduced the risks of stroke, major adverse cardiovascular events, and premature death among individuals with previous stroke or uncontrolled high blood pressure living in rural China. This study assessed the cost-effectiveness profile of the intervention. Methods: A within-trial economic evaluation of SSaSS was conducted from the perspective of the health care system and consumers. The primary health outcome assessed was stroke. We also quantified the effect on quality-adjusted life-years (QALYs). Health care costs were identified from participant health insurance records and the literature. All costs (in Chinese yuan [¥]) and QALYs were discounted at 5% per annum. Incremental costs, stroke events averted, and QALYs gained were estimated using bivariate multilevel models. Results: Mean follow-up of the 20 995 participants was 4.7 years. Over this period, replacing regular salt with salt substitute reduced the risk of stroke by 14% (rate ratio, 0.86 [95% CI, 0.77–0.96]; P =0.006), and the salt substitute group had on average 0.054 more QALYs per person. The average costs (¥1538 for the intervention group and ¥1649 for the control group) were lower in the salt substitute group (¥110 less). The intervention was dominant (better outcomes at lower cost) for prevention of stroke as well as for QALYs gained. Sensitivity analyses showed that these conclusions were robust, except when the price of salt substitute was increased to the median and highest market prices identified in China. The salt substitute intervention had a 95.0% probability of being cost-saving and a >99.9% probability of being cost-effective. Conclusions: Replacing regular salt with salt substitute was a cost-saving intervention for the prevention of stroke and improvement of quality of life among SSaSS participants.