Background: Dihydropyrimidine dehydrogenase gene (DPYD) testing is crucial in preventing toxicities from fluoropyrimidine chemotherapy. Despite benefits and established guidelines, its adoption within healthcare organizations remains inconsistent and suboptimal. We implemented a quality improvement project to improve DPYD testing prior to fluoropyrimidine chemotherapy at a community-based hospital. We aimed to increase DPYD testing for patients receiving fluoropyrimidine-based chemotherapy from 65% to 95% between July 2023 to July 2024. Balancing measures included DPYD testing turnaround time. Methods: For baseline diagnostics, manual chart review was performed on 126 patients to identify frequency of DPYD testing, and turnaround time (TAT) between May 1, 2023 to August 4, 2023. Patients were excluded if they received fluoropyrimidine-based chemotherapy prior to May 1, 2023. A multidisciplinary team including medical oncology residents and staff, pharmacists, nurses, and clinical informatics specialists worked jointly to identify and address barriers to implementation. Barriers identified included lack of established workflows and awareness of the importance of testing. Diagnostic tools utilized included Ishikawa diagrams and process mapping. The team used Plan-Do-Study-Act (PDSA) cycles to address barriers. A p-chart was used to analyze the results. Results: The baseline DPYD testing rate was 65%. Barriers identified via multidisciplinary sessions included lack of established workflow, awareness and importance of testing. PDSA cycles included education sessions to breast medical oncologists and medical oncology nurses, and development of a best-practice advisory in the electronic medical record. The percentage of eligible patients receiving DPYD testing increased from 65% to 95.8% in the total population. For breast cancer patients, the rate increased from 16.7% to 100%. For gastrointestinal cancer patients, the rate increased from 56.1% to 94.2%. Sustainability was demonstrated two months post-intervention with TAT stable between 7-8 days. Conclusions: Through PDSA cycles, we improved the frequency of DPYD testing for patients receiving fluoropyrimidine chemotherapy from 65% to 95.8%. Future work will assess changes in chemotherapy prescribing behavior in the setting of variant DPYD results, and outcomes of patients with variant DPYD testing.