Background <p>Single-session interventions offer a novel approach to improving access to evidence-based mental health services using a population-based framework for delivery. The current single-arm pilot study aimed to assess the feasibility, acceptability, and preliminary effectiveness of a single-session intervention in Mayo Clinic's primary care Integrated Behavioral Health program..</p> Methods <p>Participants were recruited from Mayo Clinic's Integrated Behavioral Health program and participated in a therapist-delivered single-session therapy intervention in primary care. The intervention could be delivered by video or in-person and was based on acceptance and commitment therapy and solution-focused brief therapy principles. Descriptive statistics and 2-tailed paired sampled t-tests were used to examine outcomes.</p> Results <p>Less than 20% of the patients contacted expressed interest in the study; however, the majority who expressed interest and screened eligible completed the single-session therapy visit (<i>N</i> = 34). Acceptability was high, as indicated by study participants expressing generally high levels of satisfaction with the single visit. Participants experienced significant increases from pre- to post-intervention in readiness for change and in self-reported capacity to generate pathways toward goals. From pre-intervention to two-week follow-up, participants experienced significant reductions in depression and anxiety symptoms, significant increases in psychological flexibility and values progress, and significant decreases in values obstruction.</p> Conclusions <p>Single-session interventions may be one helpful approach among a menu of stepped care options in primary care. Future work will benefit from ongoing exploration of the most appropriate processes for implementation of single-session interventions in primary care.</p> Trial registration <p>The study is registered at ClinicalTrials.gov (NCT06347822); Registration Date: 03/29/2024.</p>