Introduction: Osteoarthritis (OA) is one of the common causes of disabilities in adults. The prevalence of Knee Osteoarthritis (KOA) is approximately 4. 9% among people over 26, 16. 7% among people over 45, and 12. 1% among people over 60 years old. This study aims to determine the effects of Low-Level Laser Therapy (LLLT) and laser acupuncture in decreasing pain and increasing functional activity in patients with subacute and chronic KOA. Materials and Methods: In this randomized, single-blind, controlled study, the patients with grades 2 and 3 primary KOA were assigned into two experimental groups (active low-level laser and acupuncture laser) and one control group (infrared & exercise). The patients in the experimental group I (n=23) were under low-level Ga-Al– As diode laser, 830-nm continuous waves, and received laser irradiation of 30 mW/cm2 power density, 3 mW output power, 0. 1 cm2 spot size, with a total dose of 18 J and for 10 minutes on 6 acupuncture points (SP10, ST34, ST35, GB34, Xiyan, SP9) around the knee in each session. The patients in the experimental group II (n=23) received 3 J power irradiation in each cm2 in a gridding technique over a triangle-like surface of 15 cm2 over the medial, lateral, and anterior sides of the knee with a total energy density of 45 J/15 cm2 for each session. Laser therapy was applied 5 times per week for a period of two weeks (10 sessions in total). The patients in the control group (group III) were under conventional physiotherapy (superficial heat therapy and isometric knee exercises for 15 minutes every day for a similar period (10 sessions in 2 weeks). The outcome study measures were pain level at rest rated by Numeric Rating Scale (NRS), Western Ontario and McMaster Universities Osteoarthritis index (WOMAC), and Short Form of McGill Pain Questionnaire (SF-MPQ). In addition, active knee flexion and extension Range of Motions (ROMs) were measured too. These variables were evaluated at the baseline time, before the intervention, and after the intervention, on the final day of the intervention. Results: Based on statistical outcomes, a significant pain reduction by NRS and McGill, an increase in functional activity by WOMAC as well as an increase in the Range of Motion of the knee were observed in three study groups after 10 sessions. However, the result of ANOVA test showed significant difference in pain reduction among three groups and the post hoc Least Significant Difference (LSD) test showed the significant difference between laser acupuncture and conventional laser groups with the control group; the largest improvement was found in Group I. In terms of functional activity, the post hoc LSD test showed the significant difference between conventional laser and laser acupuncture groups with the control group; the largest improvement was found in Group II. No significant difference was observed among the three groups with regard to the mean values of active knee flexion and extension. Conclusion: Laser acupuncture and conventional laser are more effective in reducing pain and increasing functional activity in patients with KOA compared to conventional treatment. Clinically, laser acupuncture would appear to be superior in pain reduction.