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We performed an impact and cost-effectiveness analysis of a novel HIV service delivery model in a high prevalence, remote district of Malawi with a population of 143 800 people.A population-based retrospective analysis of 1-year survival rates among newly enrolled HIV-positive patients at 682 health facilities throughout Malawi, comparing facilities implementing the service delivery model (n = 13) and those implementing care-as-usual (n = 669).Through district-level health surveillance data, we evaluated 1-year survival rates among HIV patients newly enrolled between July, 2013 and June 2014 – representing 129 938 patients in care across 682 health facilities – using a multilevel modeling framework. The model, focused on social determinants of health, was implemented throughout Neno District at 13 facilities and compared with facilities in all other districts. Activity-based costing was used to annualize financial and economic costs from a societal perspective. Incremental cost-effectiveness ratios were expressed as quality-adjusted life-years gained.The national average 1-year survival rate for newly enrolled antiretroviral therapy clients was 78.9%: this rate was 87.9% in Neno District, compared with 78.8% across all other districts in Malawi (P < 0.001; 95% confidence interval: 0.079–0.104). The economic cost of receiving care in Neno district (n = 6541 patients) was $317/patient/year, compared with an estimated $219/patient in other districts. This translated to $906 per quality-adjusted life-year gained.Neno District's comprehensive model of care, featuring a strong focus on the community, is $98 more expensive per capita per annum but demonstrates superior 1-year survival rates, despite its remote location. Moreover, it should be considered cost-effective by traditional international standards.