Background: Proponents of mobile-bearing total knee arthroplasty believe that it has potential advantages over a fixed-bearing design in terms of diminished wear and improved motion and/or function, but these advantages have not been demonstrated in a randomized clinical comparison to our knowledge. We conducted a patient-blinded, prospective, randomized clinical trial to compare mobile-bearing and fixed-bearing cruciate-substituting total knee arthroplasties of the same design. Methods: Patients between the ages of sixty and eighty-five years were prospectively randomized to receive a cruciate-substituting rotating-platform design or a fixed-bearing design with an all-polyethylene tibial component. There were no significant differences in the demographic characteristics (mean age, 72.2 years; mean American Society of Anesthesiologists score, 2.7; mean body mass index, 31.8 kg/m2) or preoperative clinical or radiographic measures between the groups. Routine clinical and radiographic follow-up measures included the Knee Society score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form-36 (SF-36) outcome measures. Results: The results of 312 arthroplasties (136 with an all-polyethylene tibial component and 176 rotating-platform designs) in 273 patients were analyzed at a minimum of two years (mean, forty-two months) postoperatively. Although there was significant improvement in both groups, there was no significant difference between the groups with regard to the mean postoperative range of motion (110.9° and 109.1°, respectively; p = 0.21), the mean KSS clinical score (90.4 and 88.2 points; p = 0.168), or the mean KSS pain score (44.9 and 43.1 points; p = 0.108) at this follow-up point. There were ten revisions: seven because of infection, one because of patellar fracture, one because of instability, and one because of aseptic loosening. Conclusions: The two designs functioned equivalently at the time of early follow-up in this low-to-moderate-demand patient group. The rotating-platform design had no significant clinical advantage over the design with the all-polyethylene tibial component. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence. Copyright © 2009 by The Journal of Bone and Joint Surgery, Incorporated.