Objective: Patient-specific positioning guides have been designed to improve precision in total knee arthroplasty. The aim of this study is to evaluate the medium-term clinical and radiological outcomes with magnetic resonance imaging-based patient-specific positioning guides. Material and methods: We retrospectively reviewed patients from two centers treated with total knee arthroplasty performed with patient-specific positioning guides. We enrolled patients operated on between January 2011 and December 2013, with a minimum follow-up of 5 years. Preoperative and postoperative hip knee angle (HKA) and position of each component in the coronal plane were assessed. Overall malalignment was defined as an outlier of more than 3 ∘ from the neutral mechanical axis and specific malalignment as when any component showed more than 2 ∘ of deviation. Clinical outcomes were evaluated using the Hospital for Special Surgery (HSS) knee Score. Results: This study included 68 patients with a mean age of 72 years. The mean postoperative alignment (HKA) was 1 8 1. 5 ∘ and 26.5% of patients showed coronal malalignment > 3 ∘ . Regarding femoral components, 19.1% showed specific malalignment (> ± 2 ∘) , while 11.7% of tibial components were classified as outliers. The mean HSS Knee Score at final follow up was 89.2. Patients whose implants were mechanically aligned did not obtain better functional outcomes (p = 0. 3). Conclusion: In our series, the use of patient-specific positioning guides resulted in a range of mechanical malalignment, similar to conventional instrumentation results reported in the literature. [ABSTRACT FROM AUTHOR]