Background: The optimal tacrolimus trough levels after kidney transplantation (KT) and its impact on allograft outcomes remains uncertain. Evidence regarding the association with long-term outcomes is limited. Our study aimed to evaluate the relationship between time-varying periodic mean tacrolimus trough levels and composite allograft outcomes in KT recipients across five transplant centers in South Korea. Methods: Data from 10,329 patients who underwent KT during 2005–2020 was retrieved from the institutional clinical data warehouse. Two-month periodic mean was derived from outpatient tacrolimus trough levels for 2–12 months posttransplant and categorized into seven ranges. The inverse probability of treatment weighting method with stabilized weights was utilized to assess the relationship between time-varying tacrolimus levels and the 1-year composite outcome (biopsy-proven acute rejection, renal dysfunction, de novo donor-specific antibodies (dnDSA), and death-censored graft failure). We also analyzed the association between the 1-year periodic mean from 2–6 years posttransplant and the 6-year outcomes. Results: The overall incidence of the composite allograft outcome at 2–12 months and 2–6 years posttransplant was 11.2% and 23.1%. With 8 ng/mL as reference, tacrolimus levels below 3 ng/mL and 3–3.9 ng/mL were associated with a higher likelihood of developing the 1-year composite allograft outcome, while 4–4.9 ng/mL showed higher hazards of dnDSA development and graft failure. Conversely, 5–5.9 ng/mL, 6–6.9 ng/mL, and 7–7.9 ng/mL groups had lower risks of developing the composite allograft outcome. For the 2–6 year outcome, trough levels 5–5.9 ng/mL and 6–6.9 ng/mL showed benefit over 8 ng/mL (adjusted hazard ratio [aHR] 0.68, 95% confidence interval [CI] 0.53–0.87, P=0.0024; and HR 0.65, 95% CI 0.50–0.85, P=0.0012) Conclusions: This real-world multicenter study in South Korea provides important insights into the association between tacrolimus trough levels and allograft outcomes in KT recipients. The findings suggest that maintaining a target trough level of 5–7.9 ng/mL during 2–12 months posttransplant, and 5–6.9 ng/mL during 2–6 years posttransplant, is associated with better allograft outcomes.