Abstract Background To evaluate clinical characteristics, imaging findings, therapeutic approach and outcome of paediatric patients with Chronic Non-Bacterial Osteomyelitis (CNO). Methods Retrospective review of 30 children diagnosed with CNO at two tertiary care centres in Belgium. Imaging data were evaluated by blinded paediatric radiologists. Results Mean age at onset was 10.3 years and mean age at diagnosis was 11.7 years. Bone pain was the leading symptom (29/30 patients). Out of 180 symptomatic lesions, 131 were confirmed on MRI as hyperintense geographic lesions on STIR images at the metaphysis and epiphysis adjacent to growth plates of tubular bones. The most common sites of involvement were the lower limbs, spine, sternoclavicular joint and humerus. For nearly half of the patients (14/30) monotherapy with NSAIDs was sufficient to obtain remission. The remaining 16 patients received second-line therapy: bisphosphonates (n = 15/30), disease-modifying antirheumatic drugs (n = 7/30), etanercept (n = 4/30) and tocilizumab (n = 1/30). Remission was reached after a mean time of 37.6 months in 26/30 patients. The prognosis was worse for patients with spinal involvement, resulting in more long-term sequelae. Conclusions We present a multicentre paediatric cohort of 30 CNO patients. A typical pattern of bone involvement could be found on MRI. NSAIDs were administered as first-line treatment. Second-line strategies included bisphosphonates, corticosteroids, methotrexate, etanercept and tocilizumab. Trial registration Retrospectively registered. Registratienummer EC KUL: MP018023