Kidney transplant recipients are at a high risk of developing cancers after transplantation. Switching from calcineurin inhibitors to sirolimus has been shown to prevent secondary nonmelanoma skin cancer but whether everolimus with reduced exposure to calcineurin inhibitors has similar anti-cancer effects remains unknown. Therefore, we compared the risk of incident cancer over seven years of follow-up among kidney transplant recipients randomized to everolimus plus reduced exposure cyclosporine versus mycophenolate sodium and standard exposure cyclosporine. Using the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), we assessed the seven-year risk of incident cancer and other graft outcomes among a subgroup of recipients who had participated in the A2309 study using adjusted Cox proportional hazard models. Of 95 recipients, 66 were randomized to everolimus (1.5 mg or 3 mg) with reduced cyclosporine and 29 received mycophenolate sodium and standard exposure cyclosporine. Compared to mycophenolate sodium and standard exposure cyclosporine, everolimus treatment was associated with unadjusted hazard ratios of 0.28 (95% confidence interval 0.11-0.74), 0.39 (0.16-0.98) and 0.41 (0.23-0.71), respectively for nonmelanoma skin cancer, non-skin cancers and any cancers. Interestingly, the adjusted hazard ratios were 0.34 (0.13-0.91), 0.35 (0.09-1.25) and 0.32 (0.15-0.71), respectively. There was no association between treatment groups and rejection, graft loss or death. Compared to standard-exposure cyclosporine, everolimus with reduced exposure to cyclosporine may be associated with a reduced risk of cancer, particularly for non-melanoma skin cancer. Thus, if confirmed in larger patient cohorts, de novo use of everolimus with reduced exposure to calcineurin inhibitors may enable a reduction in cancer burden after transplantation.