Introduction. We report the results of revision surgery in recurrent infection after anterior cruciate ligament reconstruction (ACLR) consisting of graft canal debridement and the local application of a calcium sulfate bone substitute (CSBS) with the addition of gentamicin and vancomycin in graft canal and infected foci. Materials and methods. Three patients (3 knees) were operated due to a chronic and unsuccessfully treated knee infection after ACLR. Two patients underwent multiple previous revisions (4 and 9, respectively). In all cases, the tibial ACL graft canal and adjacent bone foci were debrided. Post debridement defects in the femur and tibia and the graft tunnel in the tibia were filled with CSBS with an addition of gentamicin and vancomycin. If the absence of the ACL graft was stated, the tibial canal was closed from the joint side with a collagen sponge with gentamicin. Results. After a follow-up of 20 to 26 months, all patients obtained a complete resolution of inflammation and CRP normalization. No side effects related to CSBS were observed. There was no deterioration in the knee function and stability compared to the pre-revision status. Conclusions. CSBS with the addition of gentamicin and vancomycin applied in the graft canal and inflammatory foci in the surrounding cancellous bone proved to be effective and unrelated to complications in chronic infection after ACLR. Level of Evidence: IV (case series).