Objective: To observe whether 10.6 mu m infrared laser moxibustion provides greater pain and stiffness relief and improves joint function in patients with knee osteoarthritis (KOA) compared with sham laser moxibustion. Methods: A total of 178 patients with KOA were randomly divided into a CO2 laser moxibustion group and a sham laser moxibustion group by block randomization method. Patients in the two groups received 10.6 mu m infrared laser moxibustion or sham laser moxibustion treatment symmetrically at bilateral Dubi (ST35), respectively. Patients in both groups received 20 min of treatment, 3 times per week for 4 weeks. Treatment effects were assessed by changes in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) before treatment, at mid-treatment (2 weeks), at the end of treatment (4 weeks), and 4 weeks after treatment. Completion time for walking 50 yards was evaluated as a secondary measurement. Results: There were no statistical differences in the WOMAC scores for pain, stiffness, and function between the two groups before treatment (P>0.05). Patients in the CO2 laser moxibustion group experienced greater improvement in WOMAC pain, stiffness, and function scores at mid-treatment, the end of treatment, and 4 weeks after treatment (P<0.05). No significant inter-group difference was found at each assessment of the 50-yard walking time (P>0.05). Conclusion: Compared with the sham laser moxibustion, 10.6 mu m laser moxibustion can significantly reduce pain and improve knee joint stiffness and function in patients with KOA.