Introduction: The aim of this retrospective controlled investigation was to analyze the short-term and long-term skeletal and dentoalveolar treatment outcomes of Function Regulator 3 (FR-3) therapy. Methods: A group of 32 subjects with Class III malocclusion treated with the FR-3 appliance of Fränkel was compared with untreated Class III controls. The first observation was prepubertal, and the long-term observation was postpubertal for all subjects. Treatment consisted of full-time wear of the appliance for about 2.5 years, followed by a retention phase with the same appliance for at least 3 years. The overall observation period was 9 years 2 months. All patients showed a good level of compliance. Active treatment and posttreatment cephalometric changes were evaluated statistically with Mann-Whitney U tests. Results: The FR-3 sample showed significant improvements in both maxillary size and position. No significant reduction in the increase of total mandibular length was recorded, but significant closures of both the gonial angle and the mandibular plane angle were found. Intermaxillary and interdental changes produced in the craniofacial skeleton were maintained successfully through the pubertal growth spurt. Conclusions: Long-term results of FR-3 therapy in patients with good compliance consisted of significant maxillary modifications and induced changes in mandibular morphology. Long-term appliance wear (more than 5 years) should be emphasized when considering treatment outcomes.