Background Standard dose ganciclovir (SD-GCV) for treatment of CMV infection/disease is 5 mg/kg every 12 hours, although higher doses (7.5–10 mg/kg every 12 hours) may be considered for resistant CMV. Literature on safety/efficacy of high dose GCV (HD-GCV) is limited. We sought to evaluate safety and clinical outcomes of SD-GCV vs HD-GCV strategies. Methods Retrospective single center study of adult SOT recipients with CMV viremia from 1/1/2017-1/31/2019 who received IV GCV therapy. Primary objective was to compare incidence of cytopenias between SD-GCV and HD-GCV. Secondary outcomes compared CMV viremia clearance, incidence of CMV disease and recurrent viremia within 30 days, granulocyte colony stimulating factor (G-CSF) use, and antiviral resistance testing rates. Results We evaluated 121 patients: 74 received SD-GCV, 47 received HD-GCV. Baseline characteristics were similar between groups. Most patients received a liver transplant (46% SD vs 36% HD) and had D+/R- CMV serostatus (55.4% SD vs 68% HD). Induction immunosuppression occurred in 75%, mostly with anti-thymocyte globulin. Median baseline CMV viral loads were similar (4620 IU/mL SD vs 7770 IU/mL HD, p=0.25). Incidence of cytopenias was similar between groups: leukopenia (43% SD vs 43% HD, p=0.96), neutropenia (15% SD vs 13% HD, p= 0.75), thrombocytopenia (24% SD vs 31% HD, p=0.62). HD-GCV did not significantly impact CMV clearance (HR: 0.79 [95% CI 0.52–1.21], p=0.27). There was no difference in incidence of CMV disease (35% SD vs 38% HD, p=0.72) or incidence of recurrent CMV viremia (15% SD vs 28% HD, p=0.098). G-CSF requirement was not different (23.7% SD vs 14.3% HD, p=0.295), however, patients on HD-GCV received more doses of G-CSF (median 2 SD vs 5 HD, p=0.001). More patients in HD-GCV group were tested for antiviral resistance: 15 (21%) SD vs 20 (43%) HD, p=0.01. Of these, there was no difference in rate of resistance detection (7/15 (47%) SD vs 11/20 (55%) HD, p=0.95). Conclusion Therapy with HD-GCV did not demonstrate increased incidence of cytopenias compared to SD-GCV, nor did we observe improved time to CMV clearance or incidence of CMV disease between groups. Opportunities exist for improving stewardship of antiviral resistance testing and use of G-CSF when considering HD-GCV therapy. Disclosures All Authors: No reported disclosures