We conducted a prospective, randomized study to compare the short-term results of minimally invasive and computer-assisted total knee arthroplasty (MICA-TKA) with those of conventional total knee arthroplasty (C-TKA) for 12-month follow-up. A total of 87 subjects who met the inclusion and exclusion criteria of the study were prospectively randomized consecutively into two groups: the C-TKA group (Group A, n = 44) and the MICA-TKA technique (Group B, n = 43). All the operations were performed by the same senior surgeon. Before surgery and at follow-up, patients were evaluated by the same observer. Tourniquet time as well as total blood loss was compared. Knee Society scores (KSSs), Knee Society functional scores (KSFSs), range of motion (ROM), and radiographic results were assessed and reported preoperatively and at 12-month follow-up. Of these patients, 82 (Group A 42; Group B 40) were available for 12-month evaluation. The two groups were found to be similar in terms of coronal mechanical axis. Similarly, the femoral rotational profile revealed that the prosthesis in Group A was implanted with similar internal rotation to Group B. The average blood loss in patients of Group B was significantly reduced as compared to patients of Group A. No significant difference was detected in terms of tourniquet time. Clinical results in Group B, with regard to ROMs and KSSs, as well as KSFSs were significantly superior to that in Group A. Based on the results obtained from this study, it is demonstrated that MICA-TKA leads to a similarly accurate restoration of leg alignment and component orientation compared to the C-TKA. Moreover, MICA-TKA produces superior clinical results to that of C-TKA. However, there is clearly a need for additional high-quality clinical trials with long-term follow-up to confirm the clinical benefits of MICA-TKA.