Infectious complications with open limb bone fractures occur in 27–30% in peaceful life and 34–75% in combat trauma. The rapid spread of multiresistant bacteria and the significant reduction in the effectiveness of antibiotics pose a serious risk of limb loss or even the patient’s life. The causes and treatment of wound infection in 96 patients with open hip and tibia fractures were analyzed, including 27 injured in peaceful life and 69 combat-injured patients. The causes of wound infections in non-combat injuries were high-energy trauma, diabetes mellitus, and anemia due to concomitant diseases. The terms of admission of the wounded with combat injuries to the level of specialized and highly specialized medical care were 4 days on average, and all of them had infected wounds. Risk factors for infectious complications of open bone fractures in military patients were the features of the wound channel in the case of high-energy bullet, mine-explosive and combined injuries, delayed qualified medical care, and delay in evacuation to a higher level of medical care in connection with the tactical situation during hostilities. Treatment included external fixation devices for fracture stabilization, staged wound debridement, negative pressure wound therapy, the use of spacers, and antibiotic therapy. Colomycin and polymyxin B were effective against gram-negative bacteria, while vancomycin targeted gram-positive bacteria. Early and adequate surgical debridement, fasciotomy to prevent compartment syndrome, fracture stabilization using an external fixation device, negative pressure wound therapy, correction of anemia and protein metabolism, and antibiotic therapy according to the sensitivity of wound microflora can reduce the risks of the development and progression of wound infection.