Donor-derived cell-free DNA (dd-cfDNA) is emerging as a noninvasive biomarker for detecting kidney allograft rejection. This study aimed to evaluate the association of dd-cfDNA with the presence, activity, and severity of kidney allograft rejection and to determine its added value beyond standard care monitoring. The study included 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States. The primary analysis involved 1,134 patients. Results showed that dd-cfDNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (AMR), T cell-mediated rejection (TCMR), and mixed rejection. In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection, independently of standard care parameters. The inclusion of dd-cfDNA in a standard care prediction model improved discrimination and calibration. These findings were confirmed in external validation cohorts, including African American patients. Additionally, dd-cfDNA showed high predictive value for detecting subclinical rejection in stable patients. The study provides insights into the potential value of dd-cfDNA as an additional tool for improving the detection of allograft rejection.Donor-derived cell-free DNA (dd-cfDNA) is emerging as a noninvasive biomarker for detecting kidney allograft rejection. This study aimed to evaluate the association of dd-cfDNA with the presence, activity, and severity of kidney allograft rejection and to determine its added value beyond standard care monitoring. The study included 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States. The primary analysis involved 1,134 patients. Results showed that dd-cfDNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (AMR), T cell-mediated rejection (TCMR), and mixed rejection. In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection, independently of standard care parameters. The inclusion of dd-cfDNA in a standard care prediction model improved discrimination and calibration. These findings were confirmed in external validation cohorts, including African American patients. Additionally, dd-cfDNA showed high predictive value for detecting subclinical rejection in stable patients. The study provides insights into the potential value of dd-cfDNA as an additional tool for improving the detection of allograft rejection.