Tibiofemoral slip velocity is a key contributor to total knee arthroplasty (TKA) component wear, yet few studies have evaluated this quantity in vivo. The aim of the present study was to measure and compare tibiofemoral slip velocities in 3 TKA designs for a range of daily activities. Mobile biplane X-ray imaging was used to measure 6-degree-of-freedom tibiofemoral kinematics and the locations of articular contact in 75 patients implanted with a posterior-stabilized, cruciate-retaining, or medial-stabilized design while each patient performed level walking, step up, step down, sit-to-stand, and stand-to-sit. Using these data, tibiofemoral slip velocity was calculated for the duration of each activity for each TKA design. The pattern of tibiofemoral slip velocity was similar for all 3 TKA designs within each activity but markedly different across the 5 activities tested, with the magnitude of peak slip velocity being significantly higher in level walking (range: 158–211 mm/s) than in all other activities (range: 43–75 mm/s). The pattern of tibiofemoral slip velocity in both the medial and lateral compartments closely resembled the pattern of tibiofemoral (knee) flexion angular velocity, with a strong linear relationship observed between slip velocity and flexion angular velocity (r = 0.81–0.97). Tibiofemoral slip velocity was invariant to TKA design but was significantly affected by activity type. Our measurements of slip velocity and articular contact locations for a wide range of daily activities may be used as inputs in joint simulator testing protocols and computational models developed to estimate TKA component wear.