Background Hypertension (HTN) is a common side effect of Tacrolimus (Tac), the first-line anti-rejection medication for kidney transplant recipients. The impact of immediate-release tacrolimus (Tac IR) dosed twice daily versus extended-release tacrolimus (Tac ER) dosed once daily on long-term blood pressure control in kidney transplant recipients remains understudied. This study aims to compare the use of Tac IR versus Tac ER in kidney transplant recipients and evaluate the effects of the different formulations on systolic blood pressure (SBP), diastolic blood pressure (DBP), and HTN crisis. Methods This retrospective cohort study at a single institution collected baseline characteristics, time-varying exposure to Tac IR vs Tac ER, SBP, DBP, HTN crisis, and confounders at each post-transplant visit. A marginal structural linear mixed-effects model was employed to analyze the longitudinal blood pressure control in kidney transplant recipients receiving Tac IR and Tac ER. Results The final analysis included 654 patients, with mean ages of 52.0 years for Tac IR and 50.3 years for Tac ER. Males constituted 56.7% in Tac IR and 55.0% in Tac ER. Notably, the Black population had 2.44 times higher odds of receiving Tac ER after adjusting for the rest of the baseline characteristics. No difference was found between longitudinal SBP (p=0.386, 95% CI: -1.00, 2.57) or DBP (p=0.797, 95% CI: -1.38, 1.06). Conclusion Our study indicates that post-transplant patients taking Tac ER exhibit no difference in chronic SBP and DBP controls compared to Tac IR.S. Karger AG, Basel.