Rare disease is a long-standing focus for PCORI. Recently, PCORI acknowledged rare disease as one of twelve Topic Themes of focus for future investment. The absence of approved treatments for many rare diseases makes comparative clinical effectiveness research of head-to-head treatment options a challenge. This session will highlight PCORI-funded rare disease comparative clinical effectiveness research studies (with one example leveraging PCORnet®, The National Patient-Centered Clinical Research Network) and engagement awards and will conclude with an equity-focused roundtable discussion of future directions for rare disease research and engagement.