Context: Access to medicines is essential in primary care, yet, nationwide, there has been a significant rise in patients’ out-of-pocket costs for medicines. In 2018, U.S. prescription drug spending was $335 billion, and 1 in 4 people had difficulty affording medicines, with heightened Congressional interest in lowering drug costs. Objective: To assess how often patients at a federally qualified health center had difficulty affording their medicines and identify strategies to routinely assess medication affordability during the clinic visit. Study Design: Cross-sectional mixed methods quantitative-qualitative quality improvement survey. Setting: Primary care internal medicine clinic at a Connecticut community health center serving 1,582 patients with Medicaid, 360 with Medicare, 750 with private insurance, and 639 without insurance in 2019. Population Studied: Fifty health center patients with primary care clinic appointments in February 2020 were surveyed using random cross-sectional sampling. Patients over age 18 who spoke English, Spanish and/or Portuguese were included and patients who did not provide consent were excluded. Intervention: Using a questionnaire in English, Spanish and Portuguese, 50 adult patients were surveyed on their ability to afford their medicines since their last clinic visit and in the past year during the clinic visit intake process. The clinic’s 18 primary care physicians were then surveyed on their clinical practice adjustments when caring for patients unable to afford their medicines and the clinic’s two 340B affiliated pharmacies were briefly interviewed to further assess medication cost barriers. Main Outcome Measure: Percent of patients unable to afford their medicines. Results: Of patients surveyed, 22% had difficulty affording their medicines in the past year and 16% had difficulty affording their medicines since their last visit. One patient paid $700 for medicines at one pharmacy, later costing $16 at another pharmacy. Of physicians surveyed, 100% wanted to know if patients cannot afford their medicines, and pharmacies noted they are not required to tell patients if discounted medication cash prices are cheaper than insurance. Conclusion: Patients often cannot afford their medicines and, while comprehensive policy reform is needed, at the clinic level, patients may benefit from a screening question asking if they can afford their medicines during each clinic visit’s routine intake process to improve medication access.