Objective:To comprehensively evaluate the clinical efficacy and safety of pulse radiofrequency therapy for knee osteoarthritis (KOA) with cardiovascular disease (CVD).Methods:A total of 132 patients with knee osteoarthritis (KOA) and cardiovascular disease (CVD) admitted to the First Affiliated Hospital of Xi′an Jiaotong University from March 2022 to February 2024 were randomly divided into two groups using a random number table method. Group A (65 cases) received ultrasound-guided pulse radiofrequency treatment of the hidden nerve, while group B (67 cases) received oral etoposide tablets and intra-articular injection of sodium hyaluronate. Basic data such as age, gender, height, weight, body mass index (BMI), knee joint function grading (K-L grading), and distribution of cardiovascular disease types were recorded between the two groups. The degree of knee joint pain [Visual Analog Scale (VAS) score] and Knee Joint Function Score (OKS), Athens Insomnia Scale (AIS) scores and incidence of complications. were compared between the two groups at 1 week, 1 month, 3 months, and 6 months after treatment.Results:The VAS score of group A showed a slow decreasing trend from 1 week to 6 months after treatment. The VAS score of group B decreased to the lowest level one week after treatment and gradually increased within 6 months after treatment. The VAS scores of both groups improved after 1 week of treatment and at 1, 3, and 6 months of treatment compared to preoperative levels ( F=703.955, P<0.001), and the degree of postoperative pain improvement in the group A was better than that in the group B ( F=106.575, P<0.001). The OKS of both groups decreased significantly after 1 week of treatment and at 1, 3, and 6 months of treatment, and the time effect was statistically significant ( F=2 233.447, P<0.001). The OKS of the group A was lower than that of group B after 1 week of treatment and at 1, 3, and 6 months of treatment, and the difference was statistically significant ( F=141.214, P<0.001). The AIS scores improved significantly after 6 months of treatment compared to preoperative levels ( F=1 044.424, P<0.001), and the group A had better AIS scores than the group B at 1, 3, and 6 months of treatment, with statistically significant differences ( F=124.864, P<0.001). There was no statistically significant difference in postoperative complications between the two groups ( P>0.05). Conclusions:Ultrasound guided pulsed radiofrequency treatment of KOA with CVD can significantly alleviate postoperative pain, improve joint mobility and sleep quality, and is more effective than traditional conservative treatment of oral etoposide tablets combined with intra-articular injection of sodium hyaluronate.