Purpose The aim of this study was to evaluate the hard and soft tissue effects and differences of the Alt-RAMEC protocol to the facemask and conventional facemask protocols in patients with unilateral cleft lip and palate. Methods This prospective study was carried out with 30 patients with unilateral cleft lip and palate with skeletal and dental class III malocclusions who were referred to a university department of orthodontics. The patients were evaluated with the cervical vertebral maturation method and divided into two groups, each consisting of 15 patients. The patients in group I (mean age 10.00 & x202f;+/- 0.73 years) were treated according to conventional facemask protocol, and the patients in group II (mean age 10.07 & x202f;+/- 2.43 years) were treated according to the Alt-RAMEC protocol before facemask application. Lateral cephalometric radiographs were evaluated by using the Dolphin Imaging Software version 11.7. The skeletal, dentoalveolar and soft tissue differences and treatment times were evaluated. Results Group II demonstrated a 5.73 degrees increase in SNA, which was statistically significant, while this increase was 3.13 degrees in group I (p & x202f;< 0.001). Results for Co-A and A-PTV showed a significant increase for group II only (group I: 1.02 & x202f;mm, 1.06 & x202f;mm, group II: 3.02 & x202f;mm, 2.21 & x202f;mm; p & x202f;< 0.05 and p & x202f;< 0.01, respectively). In addition, group II presented significant increase for the values of ANB, N-A-Pg, SN/MP, Wits, U1-SN, U1-L1, U1-PTV, U1-FHP, U6-PTV, U6-FHP, overjet, Ss-PTV, UL-PTV and UL-S line (p & x202f;< 0.001). The treatment mean times were 7.3 months in group I and 4.7 months in group II (p & x202f;< 0.01). Conclusion Applying the facemask after having followed the Alt-RAMEC protocol induced more skeletal, dentoalveolar and soft tissue changes in comparison to the conventional facemask protocol in patients with unilateral cleft lip and palate.