BACKGROUND: Randomized controlled trials (RCTs) reflect priorities established by regulators. Recently, pragmatic clinical trials (PCTs) have begun to attract interest. Unlike RCTs, PCTs aim to better inform post-regulatory decision making by using head-to-head comparisons of alternative treatments, diverse patient populations, and outcomes meaningful to patients, prescribers, and payers. OBJECTIVES: To describe how U.S. insurers and public payers perceive the value of PCTs for assessment of new prescription drugs. STUDY DESIGN: Criterion-based sample of U.S. insurers and public payers. METHODS: We gathered qualitative evidence from intensive interviews with formulary decision makers at 15 payers, representing 10 major types of U.S. payers. Prior literature and exploratory interviews informed our question selection. RESULTS: Payers viewed PCTs favorably despite wariness of drug company-sponsored trials. Payers would accept results from PCTs as part of payers' synthesis of multiple sources of evidence. Payers were enthusiastic about 2 PCT features-a diverse population (compared with the more homogeneous populations typical of RCTs) and an active comparator drug (not placebo). Payers did not anticipate that PCTs would displace their own analyses of internal data. Pharmaceutical companies' financial interest in obtaining trial results that favor their own drugs reduces PCTs' perceived value and dampens their appeal to payers; nonetheless, payers would seek PCT results and review them carefully, as they do other evidence. CONCLUSIONS: Recommendations to trial designers based on payers' views include tailoring different types of PCTs to different disease conditions, building in head-to-head comparisons in phase IIIb PCTs, and designing phase IV PCTs to include broader populations.