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The aim of this study was to assess long-term changes and describe the trajectories of oral health-related quality of life (OHRQoL) in a cohort of cleft, surgery, and standard patients who received orthodontic treatment.Standard (n = 16), cleft (n = 19), and orthognathic surgery (n = 22) patients completed the short-form of the Oral Health Impact Profile (OHIP-14) before treatment, immediately posttreatment, and approximately 5 years posttreatment.An overall reduction in OHIP-14 scores (improvement in OHRQoL) occurred after orthodontic treatment; however, this was only significant for the surgery and standard groups (P <0.05). The total OHIP-14 score increased significantly from posttreatment to 5 years follow-up for all 3 study groups (P <0.05). Relative to pretreatment, however, there were significant reductions in total OHIP-14 scores at 5 years posttreatment in the surgery group (−57.4%; P <0.05), but not in the standard sample (−24.2%; P >0.05). By contrast, the OHIP-14 score in the cleft group increased but not significantly (40.2%; P >0.05). Using a mixed model analysis, a significant interaction was detected between patient group and time (ie, study time point) (F = 6.0; P <0.0001), after adjusting for age and sex.Distinct patient groups showed different OHRQoL trajectories after orthodontic treatment. Treatment-related improvements in OHRQoL are maintained over time for surgery patients, but not for those with standard malocclusions and orofacial clefts.Different patient groups show distinct OHRQoL trajectories after orthodontic treatment.Orthognathic surgery patients experience large and sustained improvements in OHRQoL.Patients with clefting and standard malocclusion do not experience OHRQoL changes in the long term.In cleft patients, the perceived need for more surgery is associated with reduced OHRQoL.