1518 Background: Primary prophylactic colony stimulating factors (PP-CSF) are prescribed to patients undergoing chemotherapy to reduce the risk of febrile neutropenia (FN) but their benefit for regimens with intermediate FN risk is uncertain. Within a pragmatic, randomized trial of a standing order entry (SOE) intervention for prescribing PP-CSF, we designed a substudy to evaluate the effectiveness of PP-CSF for patients receiving therapy with intermediate FN risk. Methods: TrACER was a cluster randomized trial where NCI community Oncology Research Program practices were randomized to usual care (UC) or a guideline-based SOE intervention. In the primary study, sites were randomized 3:1 to a SOE of automated PP-CSF orders for NCCN-designated high FN risk chemotherapy regimens and alerts against PP-CSF orders for low FN risk regimens (intervention) versus usual care. A secondary randomization assigned intervention sites to a SOE intervention either to prescribe or not prescribe PP-CSF for patients receiving intermediate FN risk regimens. Clinicians were allowed to override the SOE. Patients age ≥18 with either breast, colorectal or non-small cell lung cancer were enrolled and followed for 12 mo. PP-CSF was defined as initiation within 24-72 hours after systemic chemotherapy. Sample size calculations were based on an FN risk reduction from 15% to 7.5%, and provided 80% power at a planned enrollment of 90 patients per site. Mixed effect logistic regression models were used to test differences between sites randomized to prescribe or not prescribe PP-CSF. Results: Between January 2016 and April 2020, 24 sites (2,287 patients) were randomized to the intervention. Among intervention sites, 12 were randomized to either SOE to prescribe or an alert to not prescribe PP-CSF for the 542 patients receiving intermediate FN risk regimens. Rates of PP-CSF use were higher among sites randomized to prescribe PP-CSF (37.1% vs 9.9%, OR = 5.90 (95% CI 1.72-20.20; p = 0.0048)). Overall, the rates of FN were low and identical between PP-CSF and no PP-CSF arms (3.7% vs 3.7%). Among patients who did not receive PP-CSF, rates of FN were also low and similar between arms (3.8% vs 4.1%). Conclusions: While implementation of a SOE intervention for PP-CSF significantly increased PP-CSF use among patients receiving intermediate risk regimens, FN rates did not differ between arms. Despite SOE, 63% of patients assigned to receive PP-CSF did not receive it. FN rates overall were lower than expected and did not differ between patients that did or did not receive PP-CSF. Although this guideline-informed SOE influenced prescribing, the results suggest that neither the SOE nor PP-CSF itself provide sufficient benefit to justify their use for persons receiving intermediate FN risk regimens. Clinical trial information: NCT02728596.