Background: For the reason of chronic toxicity, tacrolimus-sparing is an important issue to be addressed in patients with kidney transplantation (KT). Several recent studies have shown that bisphosphonate use was associated with a favorable graft outcome in patients with KT. Therefore, we investigated whether the association between tacrolimus trough levels (TTLs) and graft outcome was different according to the use of bisphosphonate in patients with KT. Methods: This retrospective study included 1,657 KT patients who received tacrolimus-based immunosuppressive therapy. Primary exposure was time-dependent cross-product term of TTL (low TTL vs. normal-high TTL with reference of 6ng/mL) and bisphosphonate use. Co-primary outcomes were graft survival defined as patients death or conversion to kidney replacement therapy and eGFR <30 mL/min/1.73 m2 . Results: During the 11211.8 person-year, graft outcomes occurred in 183 (11.0%) patients. In multivariable Cox regression anal-ysis, normal-high TTL without bisphosphonate was associated with a lower risk of graft outcome (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.43–0.87) compared to low TTL without bisphosphonate. Normal-high TTL with bisphosphonate was associated with a further lower risk of graft outcome (HR, 0.36; 95% CI, 0.16–0.83) compared to low TTL without bisphospho-nate. Low TTL with bisphosphonate was also associated with a lower risk of graft outcome (HR, 0.26; 95% CI, 0.14–0.49) com-pared to low TTL without bisphosphonate. Similar results were observed with outcome of eGFR <30 mL/min/1.73 m2 . Conclusions: The use of bisphosphonate was associated with favorable graft outcomes even in lower TTL. The addition of bisphosphonate to the conventional immunosuppressant regimen may reduce tacrolimus requirement.