A 42-year-old woman presented with anemia and complex serologic test results that included a requirement for Vel-negative red blood cells (RBCs). Rare Vel-negative units were located and transfused, but her anemia worsened. As further serologic evaluation was inconclusive, an in vivo recovery study with Vel-positive RBCs was performed. Normal 24-hour recovery of these cells resulted in removal of the Vel-negative antigen restriction and successful transfusion of the patient. Resolution of the inconclusive anti-Vel serology with an in vivo recovery study simplified the acquisition of blood for this patient and conserved rate RBC units.