To address anatomical gender differences in total knee arthroplasty (TKA) specific total knee prostheses have been developed for women. Potential benefits of these modified prostheses are currently under debate. The present study investigated whether the modified design features bring benefits compared to uni-sex TKA. A total of 80 prospectively blinded and randomized patients underwent implantation of unilateral TKAs with NexGen LPS Gender Solutions (Zimmer, Warsaw, USA, group gender-specific GS prosthesis, n = 40) or NexGen LPS Flex (Zimmer, Warsaw, USA, control group standard prosthesis ST, n = 40) The follow-up was carried out 10 days and 6 weeks postoperatively. Clinical data and the subjective assessment of quality of life were evaluated using the Knee Society Clinical Rating System (KSS), the short form 36-item health survey (SF-36) and the Western Ontario and McMaster Universities OA Index (WOMAC). The two groups showed equal values in KSS, SF-36 and WOMAC preoperatively and ten days postoperatively the GS group reached an average KSS knee score of 62.6 +/- 16.1 points (ST group 56.9 +/- 14.7, p = 0.184) and a functional score of 28.5 +/- 12.1 (ST group 24.3 +/- 15.3, p = 0.082). In the overall score the GS group reached 91.1 +/- 24.1 points (ST group 81.0 +/- 27.1, p = 0.104). The GS group reached a knee score of 85.5 +/- 14.4 points (ST group 77.8 +/- 16.8, p = 0.03) and a functional score of 68.1 +/- 20.7 points (ST group 62.3 +/- 18.5, p = 0.185) 6 weeks postoperatively. In the overall score the GS group reached 153.7 +/- 30.7 points (ST group 139.6 +/- 32.4, p = 0.048). The analysis of SF-36 and WOMAC showed no significant differences at all time points. No evidence of loosening or migration was observed in both groups. Based on the data presented, gender-specific TKA type NexGen LPS Gender Solutions has advantages in terms of early functional outcome. This result is not reflected in the patient satisfaction and is not considered to be clinically relevant.