INTRODUCTION: Antibiotic exposure is associated with worse clinical outcomes in patients receiving immune checkpoint inhibitors (ICI). We analyzed antibiotic prescription patterns in lung cancer and melanoma, two malignancies in which ICI are used broadly across stages. METHODS: We performed a retrospective cohort study of adults in the U.S. Veterans Affairs (VA) medical system diagnosed with lung cancer or melanoma from 2003 to 2016. We defined antibiotic exposure as receipt of a prescription for a systemic antibacterial agent between 6 months before and 6 months after cancer diagnosis. Demographics, clinical variables, prescriptions, and diagnostic codes were abstracted from the VA Corporate Data Warehouse. Antibiotic exposure was compared using t tests, Chi-square, and multivariate analyses. RESULTS: A total of 310,321 patients (280,068 lung cancer, 30,253 melanoma) were included in the analysis. Antibiotic exposure was more common among patients with lung cancer (42% vs. 24% for melanoma; P < .001). Among antibiotic-exposed patients, those with lung cancer were more likely to receive prescriptions for multiple antibiotics (47% vs. 30% for melanoma; P < .001). In multivariate analyses, antibiotic exposure was associated with lung cancer diagnosis (HR 1.50; 95% CI, 1.46-1.55), comorbidity score (HR 1.08; 95% CI, 1.08-1.09), non-white race (HR 1.11; 95% CI, 1.06-1.17), and female gender (HR 1.31; 95% CI, 1.24-1.37). CONCLUSION: Among cancer patients, antibiotics are prescribed frequently. Antibiotic exposure is more common in certain cancer types and patient populations. Given the negative effect antibiotic exposure has on immunotherapy outcomes, these observations may have clinical and healthy policy implications.