Background: Total knee arthroplasty (TKA) is one of the most commonly performed orthopedic surgeries in the lower extremity. However, patient dissatisfaction and functional disability are mostly experienced because of pain and limited range of motion (ROM). Although manual therapy is commonly implemented to improve ROM and modulate pain in the management of musculoskeletal disorders, there is a lack of evidence about its clinical effectiveness on postoperative TKA rehabilitation. Objective: To investigate the effectiveness of an exercise program combined with manual therapy compared with an exercise program only for pain, ROM, function, quality of life, and patient satisfaction outcomes. Design: A randomized controlled clinical trial. Setting: Rehabilitation unit of a university hospital. Participants: Forty-two patients (68.45 AE 6.3 years) scheduled for unilateral TKA as a treatment of severe osteoarthritis. Interventions: Joint and soft tissue mobilizations in addition to exercise therapy were provided to the mobilization group (n = 21) while the control group received exercise therapy only (n = 21). Main Outcome Measures: The outcome measures were numeric pain-rating scale, knee ROMs, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, 10-meter walk test (10MWT), 5-times sit to stand test (5SST), and Short Form-12 (SF-12). Results: Improvements in pain outcomes were significantly higher in the mobilization group than in the control group (P = .001, F [3, 33] = 7.06) and the between-group difference in change score was 1.3 points (P = .001). Although the between-group difference in change score was 12.8 for knee flexion at 2 months (P = .001), the overall group-by-time interactions were not significant for flexion and extension ROMs (P = .175, F [3, 33] = 1.75 and P = .57, F [2, 34] = 0.56, respectively). Additionally, there were statistically meaningful group-by-time interactions on total WOMAC score (P = .006, F [2, 34] = 5.29), 10MWT (P = .002, F [3, 33] = 5.98), and SF-12 mental component summary (P = .01, F [2, 34] = 4.92) favoring the mobilization group. Also, patient satisfaction was higher in the mobilization group (P = .02). Conclusions: A structured exercise program combined with manual therapy can be more beneficial in improving pain, function, and patient satisfaction compared to exercise program alone for postoperative TKA patients.