Radiotherapy reduces the risk of locoregional recurrence of breast cancer. As a side-effect, tissue can become hypocellular, hypovascular, and hypoxic and late radiation tissue injury can develop months or years later. Radiotherapy increases the risk of complications following secondary breast reconstruction. Hyperbaric oxygen treatment (HBOT) improves oxygenation of irradiated tissue and induces neovascularisation. This study evaluated whether the incidence of complications following secondary breast reconstruction after radiotherapy is decreased with perioperative HBOT. In this retrospective case-control chart review study, patients who underwent perioperative HBOT (n = 15) were compared to lifestyle-matched (n = 15) and radiation damage-matched (n = 15) patients who underwent secondary breast reconstruction without HBOT. The HBOT group had significantly more severe radiation damage of the breast than the lifestyle- and radiation-damage-matched control groups (scoring grade 1-4, mean 3.55 versus 1.75 and 2.89 respectively, P = 0.001). Patients underwent on average 33 sessions of HBOT (18 sessions preoperatively and 15 sessions postoperatively). There was no significant difference in the incidence of postoperative complications between the HBOT group, lifestyle-matched group and radiation damage-matched group. Logistic regression analysis showed a lower risk of postoperative complications in patients who underwent HBOT. Although the HBOT group had more radiation damage than the control groups, the incidence of postoperative complications was not significantly different. This implied a beneficial effect of HBOT, which was supported by the logistic regression analysis. Definitive conclusions cannot be drawn due to the small sample size. Future research is justified, preferably a large randomised controlled trial.