Introduction: Rasburicase is a urate oxidase enzyme used for prophylaxis and treatment of hyperuricemia associated with TLS. The recommended dose of rasburicase is 0.2 mg/kg/day for 5 days; however, recent studies have demonstrated the effectiveness of a single rasburicase dose in prophylaxis and management of hyperuricemia associated with TLS. Our institution’s TLS guideline was updated to recommend the use of a single rasburicase dose (0.2 mg/kg). The primary objective of this study was to assess the efficacy of a single rasburicase dose in controlling uric acid (UA); the secondary objective was to evaluate the impact of the institutional TLS guidelines update on consumption and cost of rasburicase. Methods: This is a single center retrospective cohort study including all patients who received rasburicase from August 2012 to March 2016 at the National Center for Cancer Care and Research (NCCCR) in Qatar. Patients were divided into 2 groups based on the prescribed number of rasburicase doses (single dose vs multiple doses). Collected data included patients’ diagnosis, laboratory parameters rasburicase dose, duration, and number of dispensed vials. UA levels within 24 hours and on day 5 of initial rasburicase dose were evaluated. Risk stratification was determined according to institutional guidelines based on disease, white blood cell count, lactate dehydrogenase level, renal function, and UA level. Results: A total of 103 patients who received rasburicase were evaluated retrospectively; rasburicase was prescribed as single dose for 65 patients (63%) and multiple doses for 38 patients (37%). The majority of patients who received rasburicase as single or multiple doses were at high risk of developing TLS, representing 68% and 84%, respectively. Baseline mean UA levels were similar in both groups: 5.4±2.9 mg/dL vs 4.7±3.2 mg/L respectively (P=.7). Normal or undetectable UA levels were observed within 24 hours in 98% of patients in the single dose group and 100% of patients in the multiple doses group. All patients in both groups had normal UA on day 5 of rasburicase with relatively similar UA levels: 1.5±1.2 mg/dL vs 0.8±1 mg/dL (P=.18). Rasburicase consumption and cost were reduced by 42.5% after the guidelines update. Conclusion: The single rasburicase dose demonstrated efficacy in controlling serum UA levels. Updating the institutional TLS guidelines had a significant impact on rasburicase consumption and led to significant cost reduction.