Background Joint loading conditions have an effect on the development and management of ankle osteoarthritis and on aseptic loosening after total ankle arthroplasty (TAA). Apart from body weight, compressive forces induced by muscle action may affect joint loading. However, few studies have evaluated the influence of individual muscles on the intraarticular pressure distribution in the ankle. Question/purposes The purpose of this study was to measure intraarticular pressure distribution and, in particular, (1) to quantify the effect of individual muscle action on peak-pressure magnitude; and (2) to identify the location of the center of pressure in the weightbearing native ankles and ankles that had TAA. Methods Peak pressure and intraarticular center of pressure were quantified during force alterations of four muscle groups (peronei, tibialis anterior, tibialis posterior, and triceps surae) in 10 cadaveric feet. The pressure was measured with a pressure sensitive array before and after implantation of a three-component mobile-bearing TAA prosthesis. Linear mixed-effects models were calculated and the y-intercept (b0) and the slope (b1) of the regression were used to quantify the size of the effect. Results Mean maximum peak pressures of 2 MPa (± 2.6 MPa) and 6.2 MPa (± 3.6 MPa) were measured for the native and TAA joint respectively. The triceps surae greatly affect the magnitude of peak pressure in the native ankle (slope b1 = 0.174; p = 0.001) and TAA joint (slope b1 = 0.416; p = 0.001). Furthermore, the force of most muscles caused a posterior and lateral shift of the center of pressure in both conditions. Conclusions Our results suggest that muscle force production has the potential to alter the pressure distribution in the native ankles and those with and TAA. Clinical Relevance Our study results help us to understand the effect of muscle forces on joint loading conditions which could be used in muscle training strategies and the design of better prosthetic components. Physical therapy or guided exercises may provide the potential to relieve areas in the joint that show signs of early osteoarthritis or reduce the contact stress on prosthetic components, potentially reducing the risk of TAA failure attributable to wear.