*Purpose: Achieving a tacrolimus therapeutic trough concentration (C₀) by post-operative day (POD) 3-7 has been associated with a reduced risk for rejection. Although FDA prescribing information recommends a weight-based initial dose, the optimal starting dose of tacrolimus is unclear. We assessed if a fixed initial dose of tacrolimus 2 mg twice daily starting pre-operatively achieved target tacrolimus C₀ by POD 3 or 7.

*Methods: We performed a single-center, retrospective review of adult primary renal transplants performed between 2017-2019. Patients received rabbit anti-thymocyte globulin or basiliximab induction and maintenance immunosuppression with tacrolimus, mycophenolate, and prednisone. The primary outcome was the proportion of patients with a tacrolimus C₀ of <7 ng/mL (subtherapeutic), 7-12 ng/mL (acceptable therapeutic), 10-12 ng/mL (optimal therapeutic), and >12 ng/mL (supratherapeutic) on POD 3 and 7. Secondary outcomes included the incidence of acute rejection at 1-year. Results are reported as descriptive statistics and evaluated with chi-square test.

*Results: 857 patients were included. On POD 3, 56.7%, 35%, 7%, and 8.3% of patients had subtherapeutic (Sub), acceptable therapeutic (AT), optimal therapeutic (OT), or supratherapeutic (Sup) tacrolimus C₀, respectively. On POD 7, 8.5%, 50.6%, 23.5%, and 41% of patients had Sub, AT, OT, or Sup tacrolimus C₀, respectively. Eighty-one (9.5%) patients had acute rejection with no difference in the incidence based on induction agent (p=0.167). Graft loss occurred in 8 (1%) patients with all-cause mortality in 12 (1.4%) patients. The 1 year acute rejection rate was 8.3%, 11.7%, 13.3%, and 8.1% on POD 3 and 4.2%, 11.8%, 14%, and 7.6% on POD 7 for patients who had Sub, AT, OT, or Sup tacrolimus C₀, respectively. There was no increase in rejection rate in patients with subtherapeutic tacrolimus C₀ at POD 3 or 7.

*Conclusions: By starting an initial fixed dose, 56.7% were subtherapeutic on POD 3 and 41% were supratherapeutic on POD 7 with dose titration. Yet, this did not correlate with increased rejection. Initiating tacrolimus at a higher dose, such as the FDA recommended dose, may help reduce the time to therapeutic tacrolimus C₀.

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