Hyperhomocysteinemia (HHCy) is considered as a risk factor for thrombosis and cardiovascular diseases. Its role in the prognosis of renal transplantation is not clear. In this cross-sectional (retrospective and prospective) study we evaluated (1) the prevalence of HHCy in renal transplant recipients (RTR), (2) its influence on thrombotic events and renal transplantation outcome, and (3) the determinants of HHCy. 382 Adult RTR on regular follow up (from June 2001 to June 2005) were selected irrespective of age, sex, donor, immunosuppression or duration after transplantation. After prior consent, fasting blood samples were collected for estimation of HCy level and for various biochemical and hematological parameters. In addition, demographic details, important post-transplant events and outcome were collected retrospectively from hospital files and prospectively on follow up. HHCy was defined as HCy level >15 µmol/L. Of 379 RTR with complete data, 253(65.5%) had HHCy. Age (p=0.001), cadaver donor (p=0.01), native kidney glomerulonephritis (p=0.002), low serum albumin (p=0.01), B12 (p=0.06), FA (p=0.05), and high serum creatinine (p=0.01) were associated with HHCy. Incidents of graft thrombosis (p=0.01), new episodes of CV events (p=0.02) and deep vein thrombosis (p=0.04) were significantly higher in RTR with HHCy. Subjects with HHCy also had lower five year patient survival (96% vs. 91%; p=0.10) and significantly poorer graft survival (94% vs. 78%; p=0.0004). When thrombotic events were included in a Cox proportional multivariate hazard ratio, the risk of death censored graft loss (HR 4.0, CI 1.8-9.0) and patient mortality (HR 4.1, CI 1.8-9.5) were significantly greater (p=0.001 and 0.001 respectively) in patients with HHCy. Prevalence of HHCy among RTR is 65%. HHCy is significantly associated with thrombotic events and poor outcome. High serum creatinine, low serum albumin, low B12 and folate levels were major determinants of HHCy.