Background: Treatment of chronic osteomyelitis (OM) usually comprises surgical excision of infected bone and soft tissue, dead space management, and soft tissue closure. When soft tissue revision results in defects too large for direct closure, assistance from plastic surgeons is needed. This study reports outcomes for patients with OM treated by plastic and orthopedic surgeons in a one-stage operation with an antibiotic-loaded biocomposite (ALB) and a local or free flap. Methods: We report a series of 11 consecutive patients with OM treated from February 2017 to September 2019. The treatment protocol included surgical debridement, tissue sampling, dead space management using ALB, stabilization as needed, and soft tissue closure with a local or free flap. Results: Mean age at surgery was 62 years (39–79), mean BMI 28 kg/m² (23–39). Multiple comorbidities were present. Local flaps were used in six patients, one reverse lateral arm flap, one soleus flap, two gastrocnemius flaps, one latissimus dorsi flap, and one fascia plantaris flap. Free flaps were used in five patients, three gracilis muscle flaps and two antero-lateral thigh (ALT) flaps. Mean follow-up was 28 months (15–42). Nine patients (81.8%) healed uneventfully after the one-stage surgical intervention, while two patients (18.2%) experienced partial or complete flap necrosis and required additional surgery. No patients required amputation, and no mortalities were reported. Conclusions: One-stage treatment of OM using ALB, performed by a multidisciplinary team, led to zero amputations in a highly comorbid population, where amputation would otherwise have been unavoidable. Level of evidence: Level IV, therapeutic study.