Background: With opioid misuse rates increasing dramatically over the past two decades, an entire generation of children faces a heightened risk of adverse physical, mental, and behavioral health outcomes. Parent-Child Interaction Therapy (PCIT) is an evidence-based intervention for children aged 2-to-7 years and their caregivers that improves parent-child relationships and child disruptive behaviors. Objective: The present study evaluated PCIT outcomes for families impacted by the opioid crisis following a state-wide PCIT dissemination project in West Virginia. Methods: PCIT-trained therapists participated in structured interviews and reported on the treatment outcomes of their cases. Using a concurrent mixed-methods design, treatment outcomes were compared for 74 opioid-affected families and 78 non-opioid-affected families. Results: Both groups demonstrated statistically significant improvements in positive parenting (p < 0.001) and reductions in negative parenting (p < 0.001) and child disruptive behavior (p < 0.001) with large effects across all outcomes (d = -2.32 to 0.83), despite the majority of cases not completing treatment. There were no significant differences in treatment outcomes between groups. Qualitative findings are presented detailing the experiences of the families affected by the opioid crisis. Conclusions: Findings demonstrate that involvement in PCIT is associated with positive parent and child outcomes for families affected by the opioid crisis. Even without a full course of PCIT, families affected and not affected by opioid use were able to reap the benefits of PCIT.