Objective: To review the pharmacokinetics, efficacy, adverse effects, and clinical trials of modified-release tacrolimus (MR-4) concerning its equivalence to non-modified-release tacrolimus. Data Sources: A PubMed/MEDLINE search was conducted (1966–July 2005) using the following terms: MR-4, tacrolimus, FK506, Prograf, transplantation, calcineurin inhibitors, and immunosuppression. Additional data sources included meeting abstracts, bibliographies from identified publications, and information from the manufacturer. Study Selection and Data Extraction: All English-language, published, randomized clinical trials evaluating MR-4 were included in this review. Clinical trials that used tacrolimus for the prevention of solid-organ graft rejection were also selected from the data sources. Data Synthesis: Studies demonstrated that MR-4 has pharmacokinetic profiles similar to those of tacrolimus in healthy volunteers, renal transplant recipients, and liver transplant recipients. Similar efficacy and safety profiles have also been demonstrated. Data also suggest that the target whole blood trough concentration range of MR-4 is similar to that of tacrolimus and that it is safe to convert from tacrolimus twice daily to MR-4 once daily using a 1:1 conversion. Conclusions: Short-term clinical trials indicated that MR-4 has efficacy and safety profiles similar to those of tacrolimus. MR-4's once-daily dosing offers an advantage over the currently available calcineurin inhibitors in preventing graft rejection. However, adherence studies with MR-4 that measure clinical and economic outcomes are needed.