69 patients scheduled for total knee arthroplasty were randomized to have the surgery performed with either a minimally invasive midvastus (MIS) approach, or a conventional medial parapatellar approach, with the assistance of computer navigation. The purpose of this study was to compare pain, range of motion (ROM), duration of surgery, intra-/post-operative blood loss, and other clinical outcomes between the two approaches over a total of 6-month follow-up. Results demonstrated that the MIS technique was associated with significantly higher pain at postoperative week 2, longer duration of surgery, and blood lost during the first 24 postoperative hours. All other outcome scores were comparable between study groups.