Parental self-efficacy, parents' beliefs in their ability to successfully parent their child, plays an important role in family outcomes when a child has autism spectrum disorder. It is important to consider therapeutic self-efficacy, one's feelings of self-efficacy regarding their implementation of an intervention, within parent-mediated interventions. The goal of this mixed methods study was to better understand factors that relate to parents' therapeutic self-efficacy when implementing a telehealth-based parent-mediated intervention. Participants were 51 parents of children with autism spectrum disorder between 17 and 83 months old. Parents reported generally high therapeutic self-efficacy, and global parental self-efficacy was significantly related therapeutic self-efficacy. Thematic analysis of parents' written reflections of the intervention's lessons identified four themes that related to therapeutic self-efficacy: the importance of a good fit between the child's skills and the intervention, the importance of a good fit between the parent's interaction style and the intervention, environmental factors support intervention use, and the importance of the child's response to the intervention. Several themes differed for parents with higher and lower therapeutic self-efficacy. Findings suggest that global parental self-efficacy plays an important role in parental therapeutic self-efficacy in parent-mediated interventions. Coaches should specifically ask about the child's skills, parent's interaction style, environmental challenges, and child's response as they support parents in learning.