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Avoiding donor-specific antibody (DSA) is difficult for sensitized patients. Improved understanding of the risk of low level DSA is needed.We retrospectively compared the outcomes of 954 patients transplanted with varied levels of baseline DSA detected by single antigen beads and B flow cytometric crossmatch (XM). Patients were grouped as follows: −DSA/−XM, +DSA/−XM, +DSA/low +XM, +DSA/high +XM, and −DSA/+XM and followed up for a mean of 4.1 ± 1.9 years (similar among groups, P = 0.49).Death-censored allograft survival was similar in all groups except the +DSA/high +XM group, which was lower at 79.1% versus 96.2% in the −DSA/−XM group (P < 0.01). The incidence of chronic antibody-mediated rejection (CAMR) based on surveillance biopsy was higher with increasing DSA (8.2% −DSA/−XM, 17.0% +DSA/−XM, 30.6% +DSA/low +XM, and 51.2% +DSA/high +XM, P < 0.01), but similar in groups without baseline DSA (8.1% −DSA/−XM vs 15.4% −DSA/+XM, P = 0.19). Having a calculated panel-reactive antibody (cPRA) of 80% or greater was independently associated with CAMR (hazard ratio, 5.2; P = 0.03) even when DSA was undetected at baseline. By 2 years posttransplant, the incidence of CAMR was 19.4% in patients with cPRA of 80% or greater and undetected DSA and negative XM at baseline.Kidney transplantation with low-level DSA with or without a low positive XM is a reasonable option for highly sensitized patients and may be advantageous compared with waiting for a negative XM deceased donor. The risk for CAMR is low in patients with no DSA even if the XM is positive. Patients with cPRA of 80% or greater are at risk for CAMR even if no DSA is detected.