BACKGROUND: Post-transplant diabetes mellitus (PTDM) has serious consequences for renal allograft survival, cardiovascular risk and patient survival. METHODS: The predictive value of a fasting plasma glucose (FPG) level and oral glucose tolerance test (OGTT) on the fifth day post-transplantation were prospectively evaluated in 359 de novo renal allograft recipients. PTDM was defined as the uninterrupted need for glucose-lowering medication for at least 3 months. RESULTS: Sixty-four patients (17.8%) developed PTDM (follow-up 42.8 +/- 16.9 months). Recipient age, body mass index (BMI), biopsy-proven acute rejection (BPAR), early graft function and proteinuria, tacrolimus-based therapy, cumulative corticosteroid dose and thiazide diuretics were associated with PTDM (univariate analysis). Multivariate logistic regression analysis identified age [OR (odds ratio): 1.05 (95% confidence interval: 1.019-1.083)], BMI [OR: 1.09 (1.013-1.189)], proteinuria on Day 5 [OR: 1.51 (1.043-2.210)] and BPAR [OR: 2.74 (1.345-5.604)] as independent risk factors for PTDM while a normal OGTT on Day 5 post-transplantation was associated with a strongly reduced risk for PTDM [OR: 0.03 (0.008-0.166)]. A similar risk reduction was conferred by a normal FPG on Day 5 [OR: 0.06 (0.012-0.338)]. OGTT had the best sensitivity (93.4%) and specificity (71.9%) with a high negative predictive value (97.6%). CONCLUSION: The Day 5 OGTT is an independent predictor of PTDM that can be used for identifying recipients at reduced risk for PTDM, taking into account the impact of independent clinical risk factors like age, BMI and BPAR (treatment). This information can help clinicians in directing therapeutic management of modifiable risk factors for PTDM after renal transplantation.