Incompatible donor/recipient pairs with broadly sensitized recipients have difficulty finding a crossmatch-compatible match, despite a large kidney paired donation pool. One approach to this problem is to combine kidney paired donation with lower-risk crossmatch-incompatible transplantation with intravenous immunoglobulin. Whether this strategy is non-inferior compared with transplantation of sensitized patients without donor-specific antibody (DSA) is unknown. Here we used a protocol including a virtual crossmatch to identify acceptable crossmatch-incompatible donors and the administration of intravenous immunoglobulin to transplant 12 HLA-sensitized patients (median calculated panel reactive antibody 98%) with allografts from our kidney paired donation program. This group constituted the DSA(+) kidney paired donation group. We compared rates of rejection and survival between the DSA(+) kidney paired donation group with a similar group of 10 highly sensitized patients (median calculated panel reactive antibody 85%) that underwent DSA(-) kidney paired donation transplantation without intravenous immunoglobulin. At median follow-up of 22 months, the DSA(+) kidney paired donation group had patient and graft survival of 100%. Three patients in the DSA(+) kidney paired donation group experienced antibody-mediated rejection. Patient and graft survival in the DSA(-) kidney paired donation recipients was 100% at median follow-up of 18 months. No rejection occurred in the DSA(-) kidney paired donation group. Thus, our study provides a clinical framework through which kidney paired donation can be performed with acceptable outcomes across a crossmatch-incompatible transplant.