A new graduate registered nurse residency program integrating human patient simulation was developed at an academic medical center. The program focused on orientation through skill-based learning, critical thinking, human factors engineering, and patient safety using simulated experiences for a wide variety of high-risk, low-frequency, as well as high-frequency, commonly occurring clinical events and situations. Structured evaluations demonstrated that simulation serves as a highly effective strategy for developing competency, confidence, and readiness for entry-into-practice. It strengthened assessment and clinical skills, and enhanced nurse residents' ability to apply critical thinking to simulated patient scenarios. The time and cost of orientation decreased while recent graduate nurse satisfaction with orientation was high.