Objective:To evaluate antibiotic prescribing in ambulatory oncology clinics and to identify opportunities to improve antibiotic use.Methods:Retrospective cohort of adult patients who received care at 4 ambulatory oncology clinics from May 2021 to December 2021. Patients were included if they actively followed with a hematologist-oncologist for a cancer diagnosis and received an antibiotic prescription for uncomplicated upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), urinary tract infection (UTI), or acute bacterial skin–skin structure infection (ABSSSI) at an oncology clinic. The primary outcome was receipt of optimal antibiotic therapy, defined as a composite of drug, dose, and duration according to local and national guidelines. Patient characteristics were described and compared; predictors of optimal antibiotic use were identified using multivariable logistic regression.Results:In total, 200 patients were included in this study: 72 (36%) received optimal antibiotics and 128 (64%) received suboptimal antibiotics. The proportions of patients receiving optimal therapy by indication were ABSSSI (52%), UTI (35%), URTI (27%), and LRTI (15%). The most common suboptimal prescribing components were dose (54%), selection (53%) and duration (23%). After adjusting for female sex and LRTI, ABSSSI (adjusted odds ratio, 2.28; 95% confidence interval, 1.19–4.37) was associated with optimal antibiotic therapy. Antibiotic-associated adverse drug events occurred in 7 patients; 6 occurred patients who received prolonged durations and 1 occurred in a patient who received an optimal duration (P= .057).Conclusions:Suboptimal antibiotic prescribing in ambulatory oncology clinics is common and mostly driven by antibiotic selection and dosing. Duration of therapy may also be an area for improvement as national oncology guidelines have not adopted short-course therapy.