Although single-radius (SR) designs of total knee replacement (TKR) have theoretical benefits, the clinical advantage conferred by such designs is unknown. The aim of this randomized, controlled study was to compare the short-term clinical outcomes of the two design rationales. A total of 105 knees were randomized to receive either a single radius (Scorpio, Stryker; SR Group) or multiple radius (AGC, Zimmer Biomet; MR group) TKR. Patient-reported outcomes (Oxford Knee Score [OKS] and Knee Society Score [KSS]) were collected at 6 weeks, 6 months, and 1 year following surgery. No knees were revised. There was no difference in primary outcomes: OKS was 39.5 (95% confidence interval [CI]: 36.9–42.1) in the SR group and 38.1 (95% CI: 36.0–40.3) in the MR group (p = 0.40). KSS was 168.4 (95% CI: 159.8–177.0) in the SR group; 159.5 (95% CI 150.5–168.5) in the MR group (p = 0.16). There was a small but statistically significant difference in the degree of change of the objective subscale of the KSS, favoring the SR design (p = 0.04), but this is of uncertain clinical relevance. The reported benefits of SR designs do not provide demonstrable functional advantages in the short term.