Background The single-radius design is one of the major total knee arthroplasty (TKA) designs and widely used all over the world. The objective of this study was to compare in vivo kinematics between the anteroposterior (AP) single-radius design with mediolateral (ML) single-radius (Non Restricted Geometry; NRG) and ML dual-radius (Triathlon) during stair activities. Methods A total of 21 knees in 18 patients (NRG group: 10 knees in 7 patients, Triathlon group: 11 knees in 11 patients) with a clinically successful posterior stabilized TKA were examined. Under fluoroscopic surveillance, each patient performed stair ascending and descending motions. In vivo kinematics were analyzed using 2D/3D registration technique. The knee flexion angle, rotation angle, varus-valgus angle, AP translation of the femorotibial contact point for both the medial and lateral sides of the knee, and post-cam engagement were evaluated. Results There were no significant differences between the two groups in rotation angle and AP translation at each flexion angle. Examining the varus-valgus angle, the NRG group showed varus position at an early flexion angle during both stair activities. Post-cam engagement was observed in both groups during both stair activities. The mean flexion angle of engagement in the NRG group, the post of which was located anterior to the Triathlon, was larger than that in the Triathlon group during both stair activities. Conclusion Despite the same AP single-radius TKA, ML single-radius might affect varus motion at an early flexion angle.