The significance of pretransplant donor-specific antibodies (DSAs) despite negative complement-dependent lymphocytotoxicity crossmatch (CDC-XM) would be useful for clinical decision-making. Hence, we aimed to determine the impact of pretransplant DSA despite negative crossmatch on the outcome of kidney transplantation. One hundred and eleven kidney recipients were prospectively enrolled in this study after being transplanted at Hamed Al-Essa Organ Transplant Center of Kuwait between January 2011 and December 2013. Of them, 50 recipients with positive DSA at the time of transplant were subjected to desensitization (Group 1). Three local protocols were utilized; first included plasma exchange, high-dose intravenous immunoglobulin (IVIG), and rituximab; second included immunoadsorption plus RTX, and the third included high-dose IVIG and rituximab. The second group included 61 recipients with negative DSA. All recipients had negative CDC-XM and flow cytometry crossmatch at the time of transplant. Panel-reactive antibody (±DSA) levels with mean fluorescence intensity and graft function were monitored along the first 24 months for all patients. There were no statistically significant differences between the two groups regarding early posttransplant graft function, patient and graft survivals. Pretransplant DSA with negative CXM carries a minimal clinical risk with optimized immunosuppression.