Background: The Cierny and Mader classification assists with decision-making by stratifying host status and the pathoanatomy of the disease. However, the anatomical type IV represents a heterogenous group with regard to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. Methods: A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Results: Risk factors for the presence of a critical bone defect were female patients [OR 3.1 (95% CI, 1.08–8.92)] and requirement for soft tissue reconstruction [OR 3.35 (95% CI, 1.35–8.31)]; osteomyelitis of the femur was negatively associated with the presence of a critical bone defect [OR 0.13 (95% CI, 0.03–0.66)]. There was no statistically significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to the bone union was ten months (95% CI, 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect [12.0 months (95% CI, 10.2–13.7 months)] and those without [6.0 months (95% CI, 4.8–7.1 months)]. Conclusion: This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time.