Uncontrolled infection, especially with multidrug-resistant bacteria, may significantly inhibit wound healing. Although negative-pressure wound therapy can help prevent infection, it is contraindicated in patients with untreated infections, including osteomyelitis. Here, we report successful wound healing by negative-pressure wound therapy in a patient with refractory osteomyelitis due to multiple multidrug-resistant bacterial infections. Soft tissue infection and osteomyelitis progressed deeply through subcutaneous tunneling; hence, bacteria were not excreted from the affected area. Negative-pressure wound therapy reduced the bacterial load and resolved the patient’s condition. Healing by secondary intention progressed with subsequent formation of granulation tissue. Despite recommendations against negative-pressure wound therapy in patients with osteomyelitis, this study highlights the application of the technique for infection control in patients with multidrug-resistant bacterial infections and osteomyelitis.