OBJECTIVES In recent years, Indigenous health curricula have been integrated into medical education in response to international calls to improve Indigenous health care. Instruments to evaluate Indigenous health education are urgently needed. We set out to validate a tool to measure self-reported medical student preparedness to provide culturally safe care to Indigenous Peoples. We then applied the tool to evaluate the effectiveness of the Northern Ontario School of Medicine University's (NOSM U) Indigenous health curriculum. METHODS We conducted psychometric testing of a 46-item draft NOSM Cultural Competency and Safety Tool (CAST). Testing included principal components analysis, subscale and item analysis, and the use of paired sample t-tests to examine pre- and posttest change to measure learner outcomes. The NOSM CAST was transposed to create a retrospective pre–posttest survey with single-point-in-time scoring. RESULTS Respondents included five cohorts of first-year undergraduate medical students, with 305 of 320 participating (response rate of 95.3%). The validated survey subscales included knowledge, confidence/preparedness, attitudes, intentions for advocacy, antidiscrimination, and self-reflective practice, measured using 36 scale items. Cronbach's alpha showed good to excellent internal consistency for the scales ( α range = 0.82–0.91). Composite reliability values were acceptable. The pre–posttest analysis showed statistically significant increases on four scales: knowledge [ t(254) = 15.10, P < .001], confidence/preparedness [ t(254) = 15.85, P < .001], intentions for advocacy [ t(251) = 3.32, P = .001], and self-reflective practice [ t(254) = 8.04, P < .001]. The largest mean increases were for knowledge ( d = 1.07) and confidence/preparedness ( d = 1.15). CONCLUSIONS The NOSM CAST tracks student progress in Indigenous health curricula. NOSM U's classroom and immersion-based Indigenous health curriculum enhanced students’ self-reported preparedness for culturally safe care. NOSM CAST implemented together with an assessment of Indigenous patient experiences with the same learners constitutes a rigorous evaluation approach to Indigenous health curricula.