PURPOSE: Cemento-osseous dysplasia (COD) is a fibro-osseous lesion whose management is highly controversial in the literature. Due to scarcity of comprehensive studies on its management, the aim of this study was to analyse its management and develop a treatment protocol. METHODS: A multi-centre retrospective cohort analysis was conducted at two tertiary referral hospitals on 124 patients diagnosed with COD from 2005 to 2023. Demographic, clinical, and radiological data were analysed and correlated with treatment methods. Post-operative complications such as osteomyelitis or pathological fracture were documented along with follow-up visits to evaluate the need for further treatment. Data was analysed using Student's t-test and Fisher's exact test. Statistical significance was set at P < 0.05. RESULTS: The patients' ages ranged from 22 to 78 years (mean: 48.5 years), with majority being females (90.4%) and of African descent (95.9%). Radiopaque CODs presented significantly higher rate of symptoms compared to radiolucent or mixed lesions (p = 0.02). The majority of incidental CODs were managed through observation (72%), while six incidental CODs underwent biopsy due to suspicion of more sinister lesions. Symptomatic lesions were mainly treated by curettage (29.7%) or local excision (48.6%), while only one symptomatic case was managed with observation and antibiotics (p = 0.0001). CONCLUSION: Biopsy of asymptomatic COD should only be reserved for cases with inconclusive clinico-pathological features. The decision to surgically treat COD should be based on the presence of symptoms and infection. Early curettage or excision of infected COD is the most effective approach to eradicate the disease and prevent progression into osteomyelitis. CLINICAL TRIAL NUMBER: Not applicable.