BACKGROUND: Initial Canadian federal regulations for the abortion pill, mifepristone, had the potential to impede safe and equitable access to this medication. To catalyze evidence-based regulatory change, we engaged health policy, health system, and health services decision makers, and health professional organizations in integrated knowledge translation (iKT), a research approach that engages the users of research as equal partners. METHODS: We conducted a realist evaluation of what iKT strategies worked, for whom, and in what context to impact federal mifepristone regulations. We constructed initial program theories (if-then statements about how iKT worked). We tested the initial program theories using interviews with researchers and knowledge partners and triangulated with analysis of research programme documents. We configured the evidence in relation to the initial program theories, and refined program theories into causal explanatory configurations. RESULTS: We analyzed 38 interviews with researchers, health professional leaders, advocacy group leaders, and administrative government policy makers, as well as 49 program documents. Our results indicated that researcher partnerships with stakeholders had a meaningful impact on the removal of restrictions. We found key components of the causal explanatory configurations included: researcher motivation to move evidence into action, trusted reputations as credible sources of evidence, strategic partnerships, understanding of health policy processes, and researcher roles as a trusted convenor between key groups and decision makers. CONCLUSIONS: Our study identifies several practical and transferable approaches to impactful iKT. The findings may be of relevance to researchers focused on public health topics subject to stigma.