Peri-prosthetic breast infections pose a risk of severe complications after breast implant surgery. The need to remove the breast implant, control the infection and perform additional surgical procedures are the consequences. Reimplantation of an alloplastic implant is only appropriate after an infection-free interval. In this retrospective cohort study, we investigated the effectiveness of negative pressure wound treatment with instillation and dwell time (NPWTi-d) on peri-prosthetic breast infections in combination with implant removal and antibiotic therapy. Twelve patients treated with NPWTi-d due to breast implant infection were included in the study. The bacterial burden was analyzed using wound swabs before and after NPWTi-d. Additionally, laboratory values were determined before NPWTi-d and immediately before wound closure. A total of 13 peri-prosthetic breast infections in 12 patients were treated using implant removal and NPWTi-d. In 76.9% (n = 10) of the cases, the patients had undergone alloplastic breast reconstruction following cancer-related mastectomy, whereas 23.1% (n = 3) of the patients had undergone breast augmentation for cosmetic reasons. The bacterial burden in the breast pocket decreased statistically significant after implant removal and NPWTi-d. No shift from Gram-positive to Gram-negative bacteria was observed. Inflammatory markers rapidly decreased following treatment. NPWTi-d had a positive impact on the healing process after peri-prosthetic breast infections, leading to a decrease in bacterial burden within the wounds and contributing to uneventful healing. Therefore, secondary reimplantation of breast prostheses might be positively influenced when compared to conventional implant removal and simple secondary closure. Further studies are required to conclusively establish the beneficial long-term effects of using NPWTi-d for the treatment of peri-prosthetic breast infections.