OBJECTIVES Rasburicase is a recombinant urate-oxidase enzyme that reduces high levels of plasma uric acid (UA) resulting from tumor lysis syndrome (TLS). Rasburicase reduces UA levels within four hours of administration, minimizing risk of serious complications from TLS. Treatment pattern analyses indicate rasburicase is often used in combination with allopurinol; however, no studies have evaluated the clinical and economic consequences of this pattern of care. This study compared hospitalization costs, length of stay, and duration of critical care in patients receiving rasburicase with or without allopurinol. METHODS Patients within the Premier hospital database administered rasburicase or combination therapy in the first two days of hospital admission were eligible for study inclusion. Patients were excluded if they were aged <18 years or received hemodialysis on admission. Patients were propensity score matched to rasburicase based on gender, race, hospital type, provider type, payer type, admission source, use of electrolyte modification therapy, critical care admission, and comorbid diagnoses. Differences in healthcare costs, length of stay, and duration of subsequent critical care were assessed using gamma distributed generalized linear models with a log link function. Projection weights were used to produce national projected patient counts. RESULTS There were 280 rasburicase and 310 combination patients matched in the analysis. The mean age was 65.2 years, with 31% being female. No statistical differences existed in matched covariates across the cohorts. Rasburicase patients incurred an average total cost of $39,245 per hospitalization compared to $52,402 for combination patients (p=0.0534). Rasburicase patients also had a lower length of stay (10.2 days) compared to combination therapy (16.1 days, p<0.0047). Duration of critical care was similar in both cohorts (rasburicase = 2.9 days vs 3.1 days, p=0.792). CONCLUSIONS Combination therapy of rasburicase and allopurinol resulted in higher total hospitalization costs and a longer length of stay compared to rasburicase monotherapy.