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Background Resident participation in quality improvement and patient safety (QIPS) programs is an essential training experience and Accreditation Council for Graduate Medical Education requirement. However, the most effective approach to achieve this is unclear. Objective We developed an experiential Quality Improvement and Patient Safety Curriculum and Resident Experience (QIPS CURE) program, which provides internal medicine (IM) residents with foundational QIPS knowledge, and evaluated its effectiveness. Methods After reviewing IM residency QIPS curricula and obtaining input from institutional stakeholders in 2013–2014, we launched a longitudinal QIPS curriculum for all 66 postgraduate year 1–3 IM residents in July 2014. The QIPS CURE included 2 major elements: didactics, delivered through a variety of sources, including online modules and workshops, and hands-on projects. We delivered this curriculum annually from 2014 to 2018. We used project completion and an attitude survey of participants to evaluate it. Results Six projects were completed in 2014–2015, and 10 projects completed yearly for the next 3 academic years. Residents presented all projects at regional meetings. Surveyed residents reported improvement in understanding (M = 5.71, SD = 1.07 pre- to M = 6.38, SD = 0.49 post-curriculum, P = .013) and competence (M = 3.31, SD = 1.18 pre- to M = 6.08, SD = 0.77, post-curriculum, P < .001) when comparing graduates of the curriculum with incoming interns. Qualitative analysis revealed perceived acquisition of skills needed to carry out successful QIPS projects. Conclusions This QIPS program was sustainable over 4 years and generally well-received by residents, with many projects completed each year.