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RATIONALE There are no pharmacologic agents that modify emphysema progression in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE Evaluate the efficacy of losartan, an angiotensin receptor blocker (ARB), to reduce emphysema progression. METHODS The trial was a multicenter randomized placebo-controlled trial, conducted between May 2017 and January 2021. Eligible participants were age ≥40, had moderate to severe airflow obstruction, ≥10 pack-years smoking, mild-moderate emphysema on high-resolution computed tomography (HRCT), and no medical indication for or intolerance of ARBs. Treatment with losartan, 100 mg daily, or matching placebo (1:1) was randomly assigned. The primary outcome was emphysema progression on HRCT over 48 weeks. Secondary outcomes included St George's Respiratory Questionnaire (SGRQ), modified Medical Research Council dyspnea scale, COPD Assessment Test, Physical Function-Short Form 20a (PROMIS 20a). RESULTS 220 participants were enrolled; 58% were men, 19% were African American; and 24% current smokers. The medians (interquartile ranges) for age were as 65 (61, 73) years, and 48 (36, 59) for percent predicted FEV1 post-bronchodilator. The mean (95% confidence interval) percent emphysema progression was 1.35% (0.67, 2.03) in the losartan group vs 0.66% (0.09, 1.23) in placebo (P = NS). CONCLUSIONS Losartan did not prevent emphysema progression in people with COPD with mild-moderate emphysema. Clinical trial registration available at www. CLINICALTRIALS gov, ID: NCT02696564.