Despite the great advances of the technology in the joint prosthesis and the high execution rate of total knee arthroplasty (TKA), there are still about 15% of clinical unsatisfactory rate in this surgery. TKAs are currently performed using a mechanical alignment of the knee, correcting varus/valgus deformities with the purpose to achieve a longer implant survivorship, but this surgical technique results in an alteration of the normal knee kinematics. Nowadays, the idea to restore the pre-arthritic alignment of the knee with the goal to obtain a normal kinematics and better functional results becomes more and more consistent and the kinematic alignment (KA) was developed as alternative to the mechanical one. The aim of this preliminary study is to analyse the functional outcomes in patients who underwent KA-TKA in the short-term follow-up and to compare them with those obtained in patients treated by the mechanical alignment (MA) TKA. Therefore, skeletally mature patients, with no history of previous knee surgical procedures, who underwent isolated TKA for knee osteoarthritis, were included in this study. The patients were prospectively divided into two homogeneous groups according to the different surgical techniques performed (KA-TKA and MA-TKA groups). Clinical and functional scores (VAS, KOOS-PS, MCS-12, Final KSS, and Functional KSS) were collected pre- and postoperatively at a mean follow-up of 3 three months. As a result, 26 patients were included in the study, with a mean age of 69.3±7.61 years old (range: 55 - 84 years old). There were 38.5% male and 61.5% female. There were 13 patients in KA-TKA and 13 patients in MA-TKA. Three months after surgery each of the scores tested demonstrated statistically significant better outcomes in KA-TKA, compared to the MA-TKA group. MCS-12 resulted comparable in the two study groups. This preliminary study compares the short-term clinical and functional outcomes between KA and MA in total knee replacement. Further studies are required to confirm these results and to extend the sample size to obtain reliable clinical evidences.