BACKGROUND: Evidence on economically efficient strategies to lower blood pressure (BP) from low- and middle-income countries remains scarce. The Control of Blood Pressure and Risk Attenuation (COBRA) trial randomized 1341 hypertensive subjects in 12 randomly selected communities in Karachi, Pakistan, to 3 intervention programs: (1) combined home health education (HHE) plus trained general practitioner (GP); (2) HHE only; and (3) trained GP only. The comparator was no intervention (or usual care). The reduction in BP was most pronounced in the combined group. The present study examined the cost-effectiveness of these strategies. METHODS AND RESULTS: Total costs were assessed at baseline and 2 years to estimate incremental cost-effectiveness ratios based on (1) intervention cost; (2) cost of physician consultation, medications, diagnostics, changes in lifestyle, and productivity loss; and (3) change in systolic BP. Precision of the incremental cost-effectiveness ratio estimates was assessed by 1000 bootstrapping replications. Bayesian probabilistic sensitivity analysis was also performed. The annual costs per participant associated with the combined HHE plus trained GP, HHE alone, and trained GP alone were $3.99, $3.34, and $0.65, respectively. HHE plus trained GP was the most cost-effective intervention, with an incremental cost-effectiveness ratio of $23 (95 confidence interval, 6-99) per mm Hg reduction in systolic BP compared with usual care, and remained so in 97.7 of 1000 bootstrapped replications. CONCLUSIONS: The combined intervention of HHE plus trained GP is potentially affordable and more cost-effective for BP control than usual care or either strategy alone in some communities in Pakistan, and possibly other countries in Indochina with similar healthcare infrastructure.