Many people develop functional limitation due to pain of osteoarthritis (OA) of the knee. Different physiotherapeutic modalities are commonly used to give treatment for patients with OA knee. This study aims to examine the efficacy of therapeutic ultrasound (UST) vs interferential therapy (IFT) to reduce pain and to improve functional ability in OA knee. Thirty subjects with a mean age of 62.55 ± 6.25 years having clinical diagnosis of OA of knee were randomly allocated to two study groups, namely groups I and II, each of 15 patients. Group I received UST and therapeutic exercise and group II received IFT and same therapeutic exercise designed for OA knee, conducted five times a week for 2 weeks. The outcome of this intervention was measured in terms of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, pain relief in terms of visual analog scale (VAS), and active range of motion (ROM). It was concluded that IFT could be the better choice of modality than UST in the management of OA of knee. Clinical significance: This study helped us to formulate a better therapeutic approach of OA of knee.