We describe a protocol for treating tire explosion injuries to the hands on the basis of treatment of five cases over a 3-year period at Emory University Hospital. These high-energy wounds frequently require emergent initial debridement and stabilization, followed by complex soft tissue and skeletal reconstruction to maximize function. Data from all cases are summarized to show similarities among these injuries and differences in their response to treatment. We define the stages of treatment, emphasizing prevention, complete assessment, and early intervention, especially for limb-threatening conditions with fasciotomy, revascularization, thorough debridement, and rigid fixation. We also discuss the importance of aggressive therapy, close follow-up, and treatment of late complications. Functional reconstruction was achieved in each case, suggesting that our treatment protocol can be used successfully.