BACKGROUND There is no accepted best practice for optimizing tertiary student knowledge, perceptions, and skills to care for sexual and gender diverse groups. The objective of this research was to synthesize the relevant literature regarding effective curricular initiatives designed to enhance tertiary level student knowledge, perceptions, and skills to care for sexual and gender diverse populations. METHODS A modified Critical Interpretive Synthesis using a systematic search strategy was conducted in 2015. This method was chosen to synthesize the relevant qualitative and quantitative literature as it allows for the depth and breadth of information to be captured and new constructs to be illuminated. Databases searched include AMED, CINAHL EBM Reviews, ERIC, Ovid MEDLINE, Ovid Nursing Database, PsychInfo, and Google Scholar. RESULTS Thirty-one articles were included in this review. Curricular initiatives ranging from discrete to multimodal approaches have been implemented. Successful initiatives included discrete sessions with time for processing, and multi-modal strategies. Multi-modal approaches that encouraged awareness of one's lens and privilege in conjunction with facilitated communication seemed the most effective. CONCLUSIONS The literature is limited to the evaluation of explicit curricula. The wider cultural competence literature offers further insight by highlighting the importance of broad and embedded forces including social influences, the institutional climate, and the implicit, or hidden, curriculum. A combined interpretation of the complementary cultural competence and sexual and gender diversity literature provides a novel understanding of the optimal content and context for the delivery of a successful curricular initiative.