:Prophylactic infusion of selected donor T cells can be an effective method to restore specific immunity after T-cell-depleted allogeneic stem cell transplantation (TCD-alloSCT). In this phase I/II study, we aimed to reduce the risk of viral complications and disease relapses by administrating donor-derived CD8pos T cells directed against cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus antigens, tumor-associated antigens (TAA) and minor histocompatibility antigens (MiHA). Twenty-seven of thirty-six screened HLA-A*02:01pos patients and their CMVpos and/or EBVpos donors were included. Using MHC-I-Streptamers, 27 T-cell products were generated containing a median of 5.2 × 106 cells. Twenty-four products were administered without infusion-related complications at a median of 58 days post alloSCT. No patients developed graft-versus-host disease during follow-up. Five patients showed disease progression without coinciding expansion of TAA/MiHA-specific T cells. Eight patients experienced CMV- and/or EBV-reactivations. Four of these reactivations were clinically relevant requiring antiviral treatment, of which two progressed to viral disease. All resolved ultimately. In 2/4 patients with EBV-reactivations and 6/8 patients with CMV-reactivations, viral loads were followed by the expansion of donor-derived virus target-antigen-specific T cells. In conclusion, generation of multi-antigen-specific T-cell products was feasible, infusions were well tolerated and expansion of target-antigen-specific T cells coinciding viral reactivations was illustrated in the majority of patients.