Background <p>The proper leveling of curve of Spee (CoS) is critical in orthodontic treatment. However, achieving a leveled CoS using clear aligner therapy (CAT), particularly in cases involving premolar extractions, poses significant challenges. This retrospective study aims to evaluate the effectiveness of clear aligners in leveling the CoS in premolar extraction and non-extraction patients, and to identify key factors influencing post-treatment CoS.</p> Methods <p>Thirty non-extraction patients and thirty patients with bilateral mandibular first premolar extractions, all of whom received CAT, were included in the study. The CoS of the pre-treatment, predicted post-treatment, and actual post-treatment dentition models were measured using Geomagic Studio software.</p> Results <p>The pre-treatment CoS showed significant correlations with overbite, overjet, and Angle classification. Both the non-extraction and extraction groups failed to achieve the predicted improvement in CoS. However, the extraction group exhibited a greater discrepancy between the predicted and actual changes (1.38 ± 0.74&#xa0;mm for the extraction group vs. 0.84 ± 0.58&#xa0;mm for the non-extraction group). The regression model indicated that the post-treatment CoS was positively correlated with pre-treatment CoS, predicted CoS, and the use of Class II intermaxillary elastics, while it was negatively correlated with initial crowding.</p> Conclusions <p>The extraction group showed less effectiveness in leveling the curve of Spee compared to the non-extraction group. The results of the regression analysis can aid clinicians in identifying factors that impact the post-treatment curve of Spee, thereby contributing to improved treatment outcomes.</p>