The opioid crisis continues to affect pregnant and postpartum women the United States, with the number of pregnant women diagnosed with opioid use disorder (OUD) quadrupling over the last decade. The associated increase in morbidity and mortality among mother and baby warrants prompt, targeted intervention efforts that improve engagement, linkage of care, and treatment retention. Patient navigation (PN) is a chronic care intervention that can directly address this need by helping women identify medical, behavioral, and psychosocial care goals. Moreover, PN can assist women in preparing for, engaging in, and maintaining patient participation in necessary services. Specifically, PN includes strengths-based case management, 1-1 clinical support, motivational interviewing, and addiction-relapse prevention programming. The objective of this article is to present the study protocol of a pilot multisite randomized clinical trial, entitled: Optimizing Pregnancy and Treatment Interventions for Moms 2.0 (OPTI-Mom 2.0; NCT03833245). In this study, we build upon a proof-of-concept study, employing evidenceinformed frameworks for protocol and intervention expansion in order to construct a PN *