Background: Pharmacokinetic data regarding a drug-drug interaction between everolimus and tacrolimus are sparse. Material/Methods: In a pharmacokinetic substudy of the randomized ASSET trial, 46 de novo kidney transplant patients receiving very low (1.5-3 ng/mL) or low (4-7 ng/mL) tacrolimus exposure after month 3, both with everolimus and steroids, provided area under the curve (AUC) concentration profiles at day 5 and months 1, 3, and 12. Results: At month 12, mean values for tacrolimus trough concentration (C-0), peak concentration (C-max), and AUC(0-12) in the very low tacrolimus group were approximately half that in the low tacrolimus group, but everolimus dose, C-0, C-max, and AUC(0-12) were virtually identical in both groups. In a cross-study comparison with data at months 1 and 3 from the pharmacokinetic substudy of the A2307 trial, in which patients received cyclosporine, mean values for everolimus C-0, C-max and AUC(0-12) were similar to those in the ASSET trial but the everolimus dose needed to achieve similar exposure was 1.5- to 2-fold higher with concomitant tacrolimus versus cyclosporine. Conclusions: Everolimus exposure is unaffected when tacrolimus exposure is down-titrated within the trough concentration range of 1.5-7 ng/mL. Higher doses of everolimus are needed to achieve a given exposure when combined with tacrolimus versus cyclosporine.