We examined physician diagnostic certainty as one reason for cross-national medical practice variation. Data are from a factorial experiment conducted in the United States, the United Kingdom, and Germany, estimating 384 generalist physicians’ diagnostic and treatment decisions for videotaped vignettes of actor patients depicting a presentation consistent with coronary heart disease (CHD). Despite identical vignette presentations, we observed significant differences across health care systems, with US physicians being the most certain and German physicians the least certain (p < .0001). Physicians were least certain of a CHD diagnoses when patients were younger and female (p < .0086), and there was additional variation by health care system (as represented by country) depending on patient age (p < .0100) and race (p < .0021). Certainty was positively correlated with several clinical actions, including test ordering, prescriptions, referrals to specialists, and time to follow-up.