Abstract Background For improved outcomes in total knee arthroplasty (TKA) correct implant fitting and positioning are crucial. In order to facilitate a best possible implant fitting and positioning patient-specific systems have been developed. However, whether or not these systems allow for better implant fitting and positioning has yet to be elucidated. For this reason, the aim was to analyse the novel patient-specific cruciate retaining knee replacement system iTotal™ CR G2 that utilizes custom-made implants and instruments for its ability to facilitate accurate implant fitting and positioning including correction of the hip-knee-ankle angle (HKA). Methods We assessed radiographic results of 106 patients who were treated with the second generation of a patient-specific cruciate retaining knee arthroplasty using iTotal™ CR G2 (ConforMIS Inc.) for tricompartmental knee osteoarthritis (OA) using custom-made implants and instruments. The implant fit and positioning as well as the correction of the mechanical axis (hip-knee-ankle angle, HKA) and restoration of the joint line were determined using pre- and postoperative radiographic analyses. Results On average, HKA was corrected from 174.4° ± 4.6° preoperatively to 178.8° ± 2.2° postoperatively and the coronal femoro-tibial angle was adjusted on average 4.4°. The measured preoperative tibial slope was 5.3° ± 2.2° (mean +/− SD) and the average postoperative tibial slope was 4.7° ± 1.1° on lateral views. The joint line was well preserved with an average modified Insall-Salvati index of 1.66 ± 0.16 pre- and 1.67 ± 0.16 postoperatively. The overall accuracy of fit of implant components was decent with a measured medial overhang of more than 1 mm (1.33 mm ± 0.32 mm) in 4 cases only. Further, a lateral overhang of more than 1 mm (1.8 mm ± 0.63) (measured in the anterior-posterior radiographs) was observed in 11 cases, with none of the 106 patients showing femoral notching. Conclusion The patient-specific iTotal™ CR G2 total knee replacement system facilitated a proper fitting and positioning of the implant components. Moreover, a good restoration of the leg axis towards neutral alignment was achieved as planned. Nonetheless, further clinical follow-up studies are necessary to validate our findings and to determine the long-term impact of using this patient- specific system.