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This prospective clinical study aimed to compare transfer accuracy and immediate loss rate of hard versus soft transfer trays utilizing a CAD/CAM workflow. We performed virtual bracket placement on intraoral scans of adolescent patients to create individual indirect bonding trays. Orthodontic software (Appliance Designer, 3Shape, Copenhagen, Denmark) was used to design the trays, which were then produced using 3D printing technology. Patients were randomly assigned to the hard or soft resin groups with a 1:1 allocation. Subgroups were determined based on the Little's Irregularity Index and distributed equally. 552 brackets were bonded onto adolescent patients using 46 CAD/CAM indirect bonding trays. The linear mean transfer errors ranged from –0.011 mm (soft) to –0.162 mm (hard) and angularly –0.255° (hard) and –0.243° (soft). No statistically significant differences were found between the subgroups or soft and hard resin groups. However, the transfer accuracy of molar brackets was significantly lower in the transversal and horizontal directions. All mean transfer errors were within the limits of clinical acceptability. The loss rate was 2.4 % in the hard resin group and 2.3 % in the soft resin group. The Intra Observer Correlation was excellent. CAD/CAM technology for indirect bracket bonding has been proven reliable in a randomized clinical trial. Both hard and soft resin showed a low rate of immediate loss compared to the current literature. Soft resin was more favorable than hard resin in terms of accuracy and usability. However, the indirect bonding of molar brackets is significantly less accurate than incisor brackets. • First clinical study evaluating transfer accuracy of 3D printed indirect orthodontic bonding trays using hard or soft material. • CAD/CAM technology was applied for digital bracket positioning and 3D printing of the transfer trays. • Hard and soft transfer trays have been shown to be accurate in a clinical setting. • Trays made of soft bonding material showed a lower rate of immediate loss and are favorable in clinical use. [ABSTRACT FROM AUTHOR]