The aim of the present retrospective study was evaluating skeletal, dental and soft tissue changes of two groups of Class II patients orthodontically treated with extractions of upper first premolars (U4 group) and upper first molars (U6 group). In total, 21 patient records (9M and 12F; mean age 12.5 ± 1.2 years) were selected for the U4 group, and 38 patient records (17M and 21F; mean age 13.2 ± 1.3 years) were recruited for the U6 group. Twenty cephalometric variables were analysed on standardised lateral cephalograms at baseline (T0) and at the end of orthodontic treatment (T1). Means and standard deviations (SDs) were calculated for both groups and increments were calculated. After revealing the normal distribution of data with the Shapiro-Wilk test, Student's -test was used to compare variables at T0 between groups. A paired -test was used to analyse changes between time points within each group, and Student's -test to compare differences between groups at T1. Both groups showed a significant increase in the distance among upper second molars and the vertical pterygoid line (PTV-maxillary second molar centroid U6 group: 6.66 ± 5.00 mm; U4 group: 3.66 ± 2.20 mm). Moreover, the distance of upper incisors to the palatal plane significantly increased (PP-maxillary incisor tip U6 group: 1.09 ± 1.52 mm; U4 group: 0.20 ± 2.00 mm; = 0.061). Significant changes were found for overjet (U6 group: -4.86 ± 1.62 mm; U4 group: -3.27 ± 1.90 mm; = 0.001). The distance between upper lip and esthetic plane showed a significantly reduction in both groups (ULip-E Plane U6 group: -2.98 ± 1.65 mm; U4 group: -1.93 ± 1.57 mm). No statistically significant changes were found in sagittal or vertical skeletal values. The significantly larger reduction of upper lip protrusion and overjet in the U6 group compared to the U4 group suggests preferring molar extraction treatment for severe Class II with protrusive soft tissues' profile and increased overjet. Since no differences on vertical values were found, an increased SN^GoGn angle should not be considered a discriminating factor for choosing molar extraction treatment.