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Objectives: The purpose of this study is to compare the effects of bee venom pharmacopuncture (BVP) therapy according to the methods used to treat knee osteoarthritis (OA): intra-acupoint combined with intra-articular injection, intra-acupoint injection, and intra-articular injection. Methods: A total of 69 patients were recruited by the Department of Acupuncture & Moxibustion at Dong-Eui Oriental University Hospital from February 1 to July 23, 2012. The patients were assigned to 3 groups: the first group with intra-acupoint combined with intra-articular BVP Injection (the experimental group), the 2nd group with intra-acupoint BVP injection (control groupⅠ), and the 3rd group with intra-articular BVP injection (control groupⅡ). The participants were assigned in the order in which they were recruited. Treatments were done twice a week, for a total of 9 times. The effectiveness was assessed by using the visual analouge scale (VAS) and the Korea Western Ontario and McMaster Universities Osteoarthritis Index (KWOMAC). Result: All three groups exhibited significant VAS and KWOMAC effects. Moreover, the follow-up at 4 weeks after the final treatment showed a persistence of BVP effects. However, when the groups were compared, no statistically significant differences in VAS and KWOMAC were noted, but when improvement was considered, the results showed that intra-articular injection was more effective than intra-acupoint injection. Especially, intra-acupoint combined with intra-articular injection was the most effective among the three treatments. Conclusion: Combining intra-acupoint with intra-articular injection, depending on the patient's symptoms, may produce better results when conservatively treating knee OA.