Objectives: In order to investigate the efficacy and safety of the newly developed herbal medicine Jetongdan, a placebo­controlled, randomized clinical trial of patients with osteoarthritis of the knee was undertaken. Methods: Data were obtained from 80 patients with OA of the knee. After enrollment, they were asked to answer a disease-specific questionnaire (Western Ontario and McMaster Universities (WOMAC) OA index) and analyzed with the erythrocyte sedimentation rate (ESR) in order to evaluate the efficacy of Jetongdan, and analyzed for aspartate transaminase (AST) level, alanine transaminase (ALT) level, blood mea nitrogen (BUN) level, and creatinine (Cr) level in order to evaluate the safety of Jetongdan. Results: The liver function and renal function did not deteriorate after treatment with Jetongdan. Composite WOMAC score and physical function subscale was improved, but pain subscale, stiffness subscale, and ESR were not improved by. This was possibly because the baseline characteristics of the two groups were not homogenized after randomization. Conclusions: Jetongdan could be a promising treatment option for osteoarthritis of the knee. Further study in a larger population with appropriate severity grades is recommended.