Due to the high prevalence of Hepatitis C virus (HCV) infection among individuals born between 1945 and 1965, in 2012 the Centers for Disease Control and Prevention began recommending HCV screening for this birth cohort. As adherence to HCV treatment is essential for sustained virologic response, identifying factors influencing medication adherence is important. The validated Adherence to Refills and Medications Scale (ARMS) is used to study recent medication adherence in those with chronic disease. This cross-sectional pilot study assesses factors associated with reduced adherence, indicated by higher ARMS scores, among individuals in this birth cohort. To elucidate factors associated with medication adherence, measured by the ARMS score, among a birth cohort at higher risk for HCV to guide future treatment and improve adherence. Patients born between 1945 and 1965, accessing care at an academic family medicine clinic, were recruited between April and June 2019. Demographics, prior HCV diagnosis, HCV risk factors (prior imprisonment, tattoos, and intravenous drug use), depression assessment (Patient Health Questionnaire-9), adverse childhood experiences (ACEs), and ARMS scores were collected. Mean ARMS scores were compared using t tests and analysis of variance (α = 0.05), while multiple variable models were performed using linear regression. Women comprised 58% of participants (n = 76), 52% reported depression and 37% 4 or more ACEs. The mean ARMS score was 16.3 (SD = 3.43) and 10% reported prior diagnosis of HCV. In the final multiple variable model, ARMS scores were 2.3 points higher in those with mild depression (95% CI: 0.63, 4.04), 2.0 in those with at least 4 ACEs (95% CI: 0.55, 3.49), and 1.8 in those with tattoos (95% CI: 0.30, 3.28). ACEs and food insecurity were identified as confounding variables in those with moderate to severe depression. This study found medication adherence was related to depression, ACEs, tattoos, and food insecurity among patients in this birth cohort at higher risk for HCV.