It was our hypothesis that patient-specific instrumentation (PSI) can improve the accuracy of the rotational alignment in TKA based on the concept of the system and on the potential to clearly identify pre-operatively during planning the classical anatomical landmarks that serve as references to set-up the rotation both for the femur and tibia. In this prospective comparative randomized study, 40 patients (20 in each group) operated in our institution between September 2012 and January 2013 by the 2 senior authors were included. Randomization of patients into one of the two groups was done by the Hospital Informatics Department with the use of a systematic sampling method. All patients received the same cemented high-flex mobile bearing TKA. In the PSI group, implant position was compared to the planed position using previously validated dedicated software. The position of the implants (frontal and sagittal) was compared in the 2 groups on standard X-rays, and the rotational position was analysed on post-operative CT-scan. 90 % of the patients add < 2A degrees or mm of difference between the planned position of the implants and the obtained position, except for the tibial rotation where the variations were much higher. Mean HKA was 179A degrees (171-185) in the PSI group with 4 outliers (2 varus: 171A degrees and 172A degrees:184A degrees and 185A degrees) and 178.3A degrees with 2 outliers (171A degrees and 176A degrees) in the control group. No difference was observed between the two groups concerning the frontal and sagittal position of the implants on the ML and AP X-rays. No significant difference of femoral rotation was observed between the two groups with a mean of 0.4A degrees in the PSI group and 0.2A degrees in the control group (p: n.s). Mean tibial rotation was 8A degrees of internal rotation in the PSI group and 15A degrees of internal rotation in the standard group (p: n.s). Based on our results, we were unable to confirm our hypothesis as PSI cannot improve rotation in TKA. More work needs to be done to more clearly define the place of PSI in TKA, to keep on improving the accuracy of the system and to better define the individual targets in TKA in terms of frontal, sagittal and rotational positioning of the implant for each patient. Prospective comparative randomized study, Level II.