Introduction Invasive cervical resorption (ICR) has an unknown aetiology, yet it exhibits very aggressive behaviour compared with typical external root resorption, posing a high risk of tooth loss. Aim To investigate the number of patients at the Dublin Cleft Prosthodontic Department with an oro-facial cleft who experienced ICR and to identify any possible aetiological factors. Materials and method A retrospective investigation of all oro-facial cleft patients treated at the Dublin Cleft Prosthodontic Department, St James’s Hospital, Dublin. All patients’ clinical and radiological records were reviewed. Patients where tooth loss became inevitable due to Class 4 ICR were analysed. Results From 588 oro-facial cleft patients, 14 (2.38%) patients with ICR were identified. Of these eight (57%) were female and six (43%) were male. Mean age at diagnosis was 28 years (range = 16–49 years). Cleft type: six (42.1%) unilateral cleft lip and palate, eight (57.9%) bilateral cleft lip and palate. Seventeen ICR affected teeth in total, with eleven (65%) maxillary central incisors, two (12%) maxillary lateral incisors, four (23%) maxillary canines, and one (7%) central, lateral and canine affected. Some, (N = 10, 71.4%) presented with ICR resulting in immediate tooth loss. Other patients (N = 4, 28.6%) developed ICR during or following prosthodontic treatment at the Cleft Centre. Tooth loss for this cohort, though not immediate, was inevitable. All had undergone fixed orthodontic appliance treatment and twelve had received dento-alveolar bone grafts. A number (N = 7, 50%) had undergone osteotomy, two (14%) had received night guard vital dental whitening and one had a history of trauma. Conclusions ICR, given its aggressive nature and ill-understood aetiology, poses significant treatment challenges. The most severe form of ICR (Class 4) leads inevitably to tooth loss. The slow–moderate progression of ICR may explain the late presentation found in this study, reinforcing the importance of long-term follow-up of this special dental care group.