Purpose To test a virtual case-based Simulated Diabetes Education intervention (SimDE) developed to teach primary care residents how to manage diabetes. Method Nineteen primary care residency programs, with 341 volunteer residents in all postgraduate years (PGY), were randomly assigned to a SimDE intervention group or control group (CG). The Web-based interactive educational intervention used computerized virtual patients who responded to provider actions through programmed simulation models. Eighteen distinct learning cases (L-cases) were assigned to SimDE residents over six months from 2010 to 2011. Impact was assessed using performance on four virtual assessment cases (A-cases), an objective knowledge test, and pre-post changes in selfassessed diabetes knowledge and confidence. Group comparisons were analyzed using generalized linear mixed models, controlling for clustering of residents within residency programs and differences in baseline knowledge. Results The percentages of residents appropriately achieving A-case composite clinical goals for glucose, blood pressure, and lipids were as follows: A-case 1: SimDE = 21.2%, CG = 1.8%, P = .002; A-case 2: SimDE = 15.7%, CG = 4.7%, P = .02; A-case 3: SimDE = 48.0%, CG = 10.4%, P < .001; and A-case 4: SimDE = 42.1%, CG = 18.7%, P = .004. The mean knowledge score and pre-post changes in self-assessed knowledge and confidence were significantly better for SimDE group than CG participants. Conclusions A virtual case-based simulated diabetes education intervention improved diabetes management skills, knowledge, and confidence for primary care residents.