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Abstract Background Reducing the burden of multidrug-resistant organism (MDRO) colonization and infection among renal transplant recipients (RTRs) may improve patient outcomes. We aimed to assess whether the detection of an MDRO or a comparable antibiotic-susceptible organism (CSO) during the early post-transplant (EPT) period was associated with graft loss and mortality among RTRs. Methods We conducted a retrospective cohort study of RTRs transplanted between 2005 and 2021. EPT positivity was defined as a positive bacterial culture within 30 days of transplant. The incidence and prevalence of EPT MDRO detection were calculated. The primary outcome was a composite of 1-year allograft loss or mortality following transplant. Multivariable Cox hazard regression, competing risk, propensity score–weighted sensitivity, and subgroup analyses were performed. Results Among 3507 RTRs, the prevalence of EPT MDRO detection was 1.3% (95% CI, 0.91%–1.69%) with an incidence rate per 1000 EPT-days at risk of 0.42 (95% CI, 0.31–0.57). Among RTRs who met survival analysis inclusion criteria (n = 3432), 91% (3138/3432) had no positive EPT cultures and were designated as negative controls, 8% (263/3432) had a CSO detected, and 1% (31/3432) had an MDRO detected in the EPT period. EPT MDRO detection was associated with the composite outcome (adjusted hazard ratio [aHR], 3.29; 95% CI, 1.21–8.92) and death-censored allograft loss (cause-specific aHR, 7.15; 95% CI, 0.92–55.5; subdistribution aHR, 7.15; 95% CI, 0.95–53.7). A similar trend was seen in the subgroup and sensitivity analyses. Conclusions MDRO detection during the EPT period was associated with allograft loss, suggesting the need for increased strategies to optimize prevention of MDRO colonization and infection.