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Background: Low immunogenicity of hepatitis B vaccine is an important problem in patients with chronic renal failure (CRF). A possible solution is intradermal versus conventional intramuscular delivery of vaccine in this population. The goal of this study was to compare the efficacy of these routes of vaccination in Bu-alicina Dialysis Center, Qazvin, Iran. Materials and Methods: This randomized clinical trial was done on 29 CRF non-responders randomly allocated to two groups. Fifteen patients received 40 μg of euvax B vaccine intradermally and 14 patients received 160 μg of this vaccine intramuscularly. Anti-HBs antibody titre was measured after 1, 6, and 12 months. Seroprotection was defined as anti-HBs antibody titre above 10 lU/L. Data were analyzed using SPSS software version 16. Results: Difference of seroprotection rate between two groups was not statistically significant after1and 6 months however, after 12 months, seroprotection rate was 93.3% in the interadermal group versus 50% in the intramuscular group (p<0.05). Conclusion: Considering the high cost of vaccination, intradermal vaccination may be a reasonable choice in CRF patients.