Due to the high risk of a bilateral total knee arthroplasty (TKR) following unilateral TKR, this study was performed to investigate bilateral TKR patients. Specifically, we examined biomechanical differences between the first replaced and second replaced limbs of bilateral patients. Furthermore, we examined bilateral TKR effects on hip, knee, and ankle biomechanics, compared to the replaced and non-replaced limbs of unilateral patients. Eleven bilateral patients (70.09 ± 5.41 years, 1.71 ± 0.08 m, 91.78 ± 13.00 kg) and fifteen unilateral TKR patients (65.67 ± 6.18 years, 1.73 ± 0.10 m, 87.72 ± 15.70 kg) were analyzed while performing level walking. A repeated measures one-way ANOVA was performed to analyze between-limb differences within the bilateral TKR group. A 2 × 2 (limb × group) ANOVA was used to determine differences between bilateral and unilateral patients. Our results showed that the second replaced limb exhibited a lower peak initial-stance knee extension moment than the first replaced limb. No other kinematic or kinetic differences were found. Bilateral patients exhibited lower initial-stance knee extension moments, knee abduction moments, and dorsiflexion moments, compared to unilateral patients. Bilateral patients also exhibited lower push-off peak hip flexion moments and vertical GRF. The differences between the first and second replaced limbs of bilateral patients may indicate different adaptation strategies used following a second TKR. The significant group differences indicate that adaptations are different between these groups, and it is not recommended to use patients with unilateral and bilateral TKR together in gait analyses.