Background: Studies have shown that erythropoietin-stimulating agents (ESAs) protect mice against the development of diabetes through direct effects on pancreatic ß cells. However, the effect of ESAs on the incidence of diabetes in humans has not been well studied. It is unknown whether exposure to ESAs is associated with a reduced incidence of new-onset diabetes after transplant (NODAT). Objective: The objective of this study is to examine the relationship between ESA exposure post-renal transplant and the development of NODAT. Design: We performed a single center, retrospective cohort analysis. Patients: We compared patients who received a first live or deceased donor renal allograft, with any exposure to an ESA vs. those without such exposure and who developed NODAT and who did not. Patients with a prior history of diabetes mellitus or multi-organ transplant, including a second renal transplant were excluded. Measurements and methods: NODAT was defined based on the 2008 Canadian Diabetes Association criteria. Multivariate logistic regression analysis was performed to determine factors independently associated with NODAT. Results: One hundred thirty-two (29 %) patients were exposed to an ESA, four of which developed NODAT compared to 128 who did not develop NODAT ( p < 0.0001). Of those not exposed to an ESA, 15 % (48/319) developed NODAT. By Fisher's exact test, exposure to an ESA at any time post-transplant reduced the risk of developing NODAT; odds ratio (OR) = 0.08, 95 % confidence interval (CI) (0.018–0.352), p = 0.0008. Older age; OR = 1.41, 95 % CI (1.036–1.933), p < 0.02, higher random blood sugar at discharge; OR = 1.30, 95 % CI (1.077–1.57), p < 0.006 and deceased donor; OR 2.18 CI (1.009–4.729), p = 0.04 were associated with an increased risk of NODAT. Limitations: The limitations of this study include its retrospective nature, single center, and homogenous population; thus, generalizability of the results must be approached with caution. Conclusion: ESA exposure may be associated with a reduced incidence of NODAT in the post-renal transplant population. The role of ESA in preventing NODAT requires further investigation.