Cladribine induces durable complete remission (CR) in approximately 85% of hairy cell leukemia (HCL) patients. In Egypt, cladribine is mainly used as IV continuous infusion at a dose of 0.1 mg/kg/day for 7 days and as SC bolus injection at a dose of 0.14 mg/kg/day for 5 days. We aimed to compare the outcome and toxicity between these two regimens. We retrospectively collected data of HCL patients treated at the National Cancer Institute and its affiliated center, Nasser Institute, Cairo, Egypt. Forty nine patients were identified, 18 treated with the IV regimen (IV group) and 31 with the SC regimen (SC group). Forty-one patients were newly diagnosed. Patient characteristics were balanced across the two groups. The CR rates in the IV and the SC group were 94% and 97%, respectively. The main complications in the IV group and the SC were neutropenia G3-4 (67% vs 87%), mucositis mainly G1-2 (67% vs 32%) and infections (mainly viral, 78% vs 34%). In the IV group, 5 patients died, 3 of progression and infection, one of unknown cause and one of late heart failure. In the SC group, one patient died of disease progression and one of second cancer. After 33.5 months median follow up, the 3-year event free survival was 60% and 96%, respectively (p=0.104). The 3-year overall survival was 81% and 100%, respectively (p=0.277). Lymphadenopathy and/or hepatomegaly may have negative influence on DFS. In conclusion, SC cladribine is an excellent alternative to the IV regimen for the treatment of HCL.  Key words: 2-chlorodeoxyadenosine, cladribine, hairy cell leukemia, intravenous, subcutaneous