Background <p>The objective was to evaluate the outcomes of orthodontic treatment following two or four first premolar extractions using the ABO-OGS and potential influencing factors.</p> Methods <p>This study included 100 patients treated with upper two-premolar extractions (TPE) (mean age: 14.7 ± 2.3) and 85 patients treated with four-premolar extractions (FPE) (mean age: 14.5 ± 3.0). Pretreatment parameters, cephalometric radiographs, and dental casts were evaluated. Patient cooperation was assessed based on regular appointment attendance, elastic use, recurrent bracket failures, and oral hygiene.</p> Results <p>There were no significant differences between TPE and FPE groups in pretreatment age, case complexity according to ABO-DI, or treatment duration. Total OGS scores were comparable between the two groups; however, marginal ridges were better aligned in the TPE group (<i>p</i> = 0.005). In both groups, pretreatment lip properties and additional mechanical requirement were associated with the total OGS score (<i>p</i> &lt; 0.05). Additionally, in the TPE group, inadequate lip-closure and curve of Spee depth affected the total OGS score, whereas U1-PP angle had an impact in the FPE group (<i>p</i> &lt; 0.05). In the TPE group, patients who didn’t attend appointments regularly had higher interproximal contact scores, and those who didn’t use elastics regularly had higher total OGS and occlusal relationship scores (<i>p</i> &lt; 0.05). In the FPE group, patients with recurrent bracket failures had higher total OGS, tooth alignment, and occlusal relationship scores (<i>p</i> &lt; 0.05). Poor oral hygiene was associated with higher occlusal contact scores (<i>p</i> &lt; 0.05).</p> Conclusions <p>Pretreatment factors, including incisor proclination, lip properties, additional mechanical requirement, and patient cooperation during treatment, influenced treatment outcomes in patients treated with TPE and FPE.</p> Trial registration <p>D-KA24/28.</p>