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Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, being a putative steatogenic factor, may promote liver fibrosis progression in patients with chronic hepatitis C. This study aimed to verify the role of recipient MTHFR polymorphism in favouring graft fibrosis progression in patients with recurrent HCV after orthotopic liver transplantation (OLT).We studied 63 such patients, followed for >1 year. MTHFR allelic variants were determined by a polymerase chain reaction/restriction fragment length polymorphism method.Recipients carrying the TT genotype had more frequently, 1-year post-OLT, homocysteine serum levels >23 μmol/L (P<0.05), serum triglycerides >180 mg/dL (P<0.02) and de novo diabetes mellitus (P<0.05) but not a higher frequency of graft steatosis. Time-to-event analysis in reaching an Ishak staging score >2 was performed by stratifying the recipients as follows: (a) patients with donor age ≤45 years, (b) patients with donor age >45 and C/* genotype, and (c) patients with donor age >45 years and TT genotype. A significant linear trend was observed, with increasing frequencies as follows: (a) 8/37, (b) 10/19 and (c) 6/7 (P=0.0005).The MTHFR C677T polymorphism may play a role in influencing liver fibrosis progression in patients with recurrent hepatitis C, in conjunction with donor age, but not via steatosis promotion.