Background: Prophylaxis for highly emetogenic chemotherapy (HEC) is well established in clinical guidelines, but real-world treatment patterns are unclear. Today, consistent use of prophylaxis is more easily accomplished due to the incorporation of ordering premeds into the workflow prior to administration of intravenous chemotherapy. However, prescription of oral agents for treatment of breakthrough chemotherapy induced nausea and vomiting (CINV) is less consistent and standardized and has a scant evidence base. In an effort to standardize utilization, we evaluated the use of prophylaxis and oral breakthrough medications in a large national community oncology network. Methods: Data from electronic medical records at five practices comprising over 100 clinic sites was analyzed to examine the frequency of guideline-recommended triplet 5-HT3 receptor antagonist, NK-1 receptor antagonist, and corticosteroid use for prophylaxis prior to the administration of HEC agents. Oral breakthrough medication use and preference was also analyzed. Data was collected and analyzed at the practice level. Results: We identified 2645 patients that received HEC between 1/1/2019 and 5/8/2020. We found consistently high utilization of guideline-concordant triplet prophylaxis regimens for patients receiving HEC, ranging from 90-100% at each of the five practices. In addition, most patients (mean 83%, range 67% - 94%) received a prescription for at least one oral breakthrough medication, but the agent(s) utilized varied widely across practices (Table). Ondansetron was the most commonly prescribed oral breakthrough medication (mean 68%, range 53% - 88%), while olanzapine use for either prophylaxis or breakthrough CINV across practices ranged from 1% - 4%. Conclusions: In this national community oncology network, standard recommended triplet agent prophylaxis for HEC was delivered successfully. However, opportunity exists to increase appropriate use of olanzapine and reduce variation of oral breakthrough antiemetic medications in order to optimize clinical care.