Introduction: This research aimed to evaluate the impact of orthodontic treatment on a young person's oral health-related quality of life, self-esteem, and esthetics concerning hypodontia. Methods: A prospective longitudinal hospital-based study recruited 97 participants with hypodontia, aged 11-18 years. Forty-one participants (42%) originally planned to have space closure and the remainder space opening, with subsequent prosthetic replacement. The following questionnaires were completed before and after orthodontic treatment: the child perception questionnaire, Bristol condition-specific questionnaire for hypodontia (BCSQ), the child health questionnaire, and the Oral Aesthetic Subjective Impact Scale (OASIS). The Wilcoxon and matched pairs t tests approach was applied to compare before and after orthodontic treatment for significant testing (P <0.05). Results: Fifteen participants were lost to follow-up, resulting in 82 participants completing orthodontic treatment, with an average age of 13.8 +/- 1.71 years. A total of 282 teeth were missing in the sample. Treatment resulted in significantly lower indexes (P <0.001) to overall BCSQ, OASIS, appearance, and how others would treat them. In comparing the 2 subgroups, those treated with space closure had significantly reduced functional limitations (child perception questionnaire), appearance concerns, self-esteem (child health questionnaire), OASIS, and overall BCSQ scores. Conclusions: Orthodontic treatment participants with hypodontia appears to significantly impact a range of psychological and esthetic scales. In particular, space closure appears to significantly improve the quality of life of participants compared with those undergoing space opening. (Am J Orthod Dentofacial Orthop 2023;164:813-23)