*Purpose: Observational and meta-analytic studies have associated sirolimus with an increased risk of mortality in kidney transplant (KT) recipients (KTRs). We aimed to examine the impact of the timing of regimen initiation on the above outcome.

*Methods: Using 2000-2016 SRTR data, Cox multivariable regressions were used to analyze the 5-year mortality associated with early initiation (from discharge post-KT) vs. late initiation (conversion at 6 months post-KT) of SRL + tacrolimus (SRL-TAC), SRL+ cyclosporine (SRL-CSA), or SRL+ mycophenolate (SRL-MPA) compared with tacrolimus + mycophenolate (TAC-MPA) regimen in the age-stratified (18-49-year-old; 50-64-year-old; and >65-year-old) cohorts

*Results: In the pooled analysis, all SRL regimens were associated with higher mortality risk than TAC-MPA , but this applied only with early, not late initiation of regimen (Fig. 1).

Stratified analyses showed that compared with KTRs on TAC-MPA in similar age cohort:

1. 18-49-yr.old KTRs had higher mortality risk with early, not with late initiation of any SRL regimen (Fig.2 & 3). Comparing same regimens, late initiation is better than early initiation of SRL-MPA and SRL-TAC (Fig.3),

2. 50-64-yr.-old KTRs had higher mortality risk with early, not with late initiation of SRL-MPA or SRL-CSA (Fig.2 & 3). Comparing same regimens, late initiation is better than early initiation of SRL-MPA and SRL-CSA (Fig.3),

3. >65-year-old KTRs had higher mortality risk with early initiation of SRL-MPA or SRL-TAC. Comparing same regimens, early initiation is better than late initiation of SRL-CSA (Fig.2).

*Conclusions: SRL regimens are associated with higher risk of mortality than TAC-MPA in adult KTRs, but regimen-and-age-specific initiation time may reduce this risk.

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