Reconstructive surgery with flaps and grafts (including microvascular anastomosis) is an evolving aspect of onco-surgery. Vascular compromise, especially inadequate arterial flow, can lead to graft failure, leading to repeated surgery, post-operative complications, and morbidities. Complications are more if the receiving tissue bed already has poor vascularity due to different local side complications such as post-radiation, chronic infection, non-healing wounds, and so on. Hyperbaric oxygen therapy at a dose of 2–2.5 atmospheric pressure can be used either as an add-on treatment modality prophylactically for compromised vascular supply or as a salvage therapeutic option. It acts by improving dissolved oxygen in blood and eventually improving tissue oxygen concentration, causing vascular endothelial growth factor-induced neovascularization at the graft base, and by decreasing ischemia–reperfusion injury. Randomized controlled trials are lacking; they show good outcomes in different kinds of compromised grafts and flaps as a rescue therapy.