AbstractLoss to follow-up (LTFU) in high-resolution anoscopy (HRA) programs jeopardizes the procedure’s potential to help prevent anal cancer. We explored quality improvement factors to understand how to address this LTFU. Using the transtheoretical COM-B Model (Capability, Opportunity, Motivation, and Behavior) and a sequential explanatory mixed-methods design, we surveyed and interviewed 13 patients who remained engaged in HIV care but who delayed their HRA monitoring or treatment visits in the same community clinic, and 6 HRA clinicians and medical assistants. Analyses involved descriptive statistics and rapid qualitative analysis. Patients were racially, ethnically, and economically representative of the LTFU population, and were generally experienced with HRA (Mean HRA visits = 4.6, SD = 2.8, mdn = 3). Providers were experienced clinicians and medical assistants (Mean years providing HRA = 6.0, SD = 2.2). Analyses revealed two primary, related barriers: (A) motivational barriers such as physical pain, discomfort, embarrassment, and anxiety; which were largely borne from (B) opportunity barriers such as difficulties with scheduling, inconsistent after-care (particularly for pain and discomfort), anxiety-inducing exam rooms and equipment, and internalized and anticipated stigma. Capability barriers, such as limited health literacy about HRA, were less common and, like motivational barriers, linked to opportunity barriers. Participants recommended potential facilitators, including easier scheduling, standardization of pain management and after-care services, and examination room modifications to reduce anxiety. To retain HRA patients in community settings, interventions should address social and physical opportunity barriers that strongly determine motivational and capability barriers. Improving convenience, standardizing pain management, and introducing stigma interventions specific to HRA, could alleviate both motivational and capability barriers.