Background: NCCN Guidelines recommend erythropoietic stimulating agents (ESAs) to manage symptomatic anemia in patients with lower-risk myelodysplastic syndrome (MDS) and serum EPO ≤500 mU/mL.Epoetin alfa and darbepoetin alfa have been used with a variety of dosing strategies in clinical practice, and patients often require dose adjustments to achieve an optimal clinical response, including transfusion independence. The objective of this study was to increase concordance with guidelines supported initial and subsequent doses of ESAs in The US Oncology Network (The Network). Methods: The Network developed a dosing guidance tool to standardize ESA dosing for anemia associated with MDS. These updates were made to the electronic health record (eHR) in October 2022 and included creation of an MDS-specific ESA regimen. The primary endpoint of initial dose concordance was evaluated in a retrospective chart review of patients with MDS, initiating treatment with an ESA, and randomly selected prior to and after implementation of the eHR changes. Secondary endpoints included subsequent ESA dose concordance at 4-weeks and 8-weeks post-implementation, percent of patients who reached hemoglobin (Hb) goal ≥10 g/dL by week 12, number of ESA orders using the MDS-specific regimen, and number of patients with transfusions after start of ESA. Fisher’s exact test was used to analyze the primary endpoint, and descriptive statistics were used for secondary endpoints. Darbepoetin claims data from five practices was also used to evaluate changes in payment denials during the intervention period. Results: The analysis included 50 patients (25 pre and 25 post). The primary outcome of overall initial dose concordance was 36% and 48% pre- and post-implementation periods respectively. The initial dose concordance was 73% vs. 29% (P=0.0472) in the group of patients who received an ESA using the new MDS-specific regimen (n=11) vs. non-MDS specific (n=14). Additionally, any ESA dose concordance (initial, 4-week post-, or 8-week post-ESA) using MDS-specific regimen vs. non-MDS specific occurred in 91% and 43% of patients post-implementation. The secondary outcome of Hb goal reached and percent transfused was 32% and 48% vs. 44% and 32% pre- and post-implementation respectively. During the study post-implementation period, first denial claims for darbepoetin decreased by 41%. Conclusions: Modification of ESA regimens to include MDS-specific dosing guidance resulted in a 12% increase in the initial dose concordance. A 48% increase in any dose concordance was noted when using MDS-specific ESA regimens vs. non-MDS specific ESA regimens. Based on these findings, additional eHR changes were implemented to increase the use of MDS-specific ESA regimens, and impact data are pending.