Tixagevimab/cilgavimab is a cocktail of two long-acting monoclonal antibodies approved for pre-exposure prophylaxis (PrEP) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (cause of coronavirus disease 2019 [COVID-19]) in immunocompromised (IC) or high-risk patients. We investigated the patient characteristics and clinical outcomes of IC patients administered tixagevimab/cilgavimab for PrEP in real-world use in Japan. This observational study used anonymous secondary data from Real-World Data Co., Ltd. for IC patients aged ≥12 years administered tixagevimab/cilgavimab between September 2022 and September 2023. We analyzed the baseline characteristics and event-rates of COVID-19-related clinical outcomes within 6 months of administration. Data were analyzed for 397 IC patients. About half (53.4%) were male and the median age was 71.0 (interquartile range 61.0, 77.0) years. Malignancy (97.2%), cardiovascular disease (71.3%), and diabetes (66.5%) were frequent comorbidities. Systemic corticosteroids and immunosuppressants were prescribed to 87.4% and 24.9%, respectively. The two most common target clinical conditions were active therapy for hematologic malignancies (88.2%) and treatment with B cell-depleting therapies (57.4%). The event-rates per 100 person-months (95% confidence interval; number) for medically attended COVID-19, COVID-19 hospitalization, in-hospital mortality due to COVID-19, and all-cause death were 4.14 (3.06-5.48; n=49), 1.74 (1.09-2.64; n=22), 0.07 (0.00-0.42; n=1), and 0.60 (0.26-1.17; n=8), respectively. This is the first report using a multicenter database to describe the clinical characteristics and COVID-19-related outcomes of IC patients administered with tixagevimab/cilgavimab in real-world settings in Japan. This cohort of IC patients who received tixagevimab/cilgavimab included many elderly patients with comorbidities.