Background: The clinical outcome of aligner therapy is closely related to the precision of its setup, which can be manually or digitally fabricated. The aim of the study is to investigate the suitability of manual setups made for aligner therapy in terms of the precision of tooth movements. Methods: Six dental technicians were instructed to adjust each of eleven duplicate plaster casts of a patient models as follows: a 1 mm pure vestibular translation of tooth 11 and a 15° pure mesial rotation of tooth 23. The processed setup models were 3D scanned and matched with the reference model. The one-sample Wilcoxon signed-rank test (p < 0.05) was used for evaluation. Results: The overall precision of the translational movement covers a wide range of values from 0.25 to 2.26 mm (median: 1.09 mm). The target value for the rotation of tooth 23 was achieved with a median rotation of 9.76° in the apical-occlusal direction. Unwanted movements in the other planes also accompanied the rotation. Conclusions: A manual setup can only be fabricated with limited precision. Besides the very high variability between technicians, additional unwanted movements in other spatial planes occurred. Manually fabricated setups should not be favored for aligner therapy due to limited precision.