Abstract Background Osteoarthritis (OA) is a common joint disorder, with the knee being one of the most frequently involved sites. Knee OA causes pain and stiffness and can lead to considerable disability and consequently to a reduced quality of life (Wideman et al. 2014). The level of radiographic knee OA is, at most, moderately associated with the level of pain. Therefore, it is unlikely that pain is predominantly caused by only bone and cartilage pathology. Mechanical, structural, inflammatory, bone-related, neurological and psychological factors play a role in the process that results in painful knee OA (Wenger et al. 2013). As OA is a disease of the entire joint that is characterised by cartilage breakdown, subchondral bone alterations and formation of osteophytes, as well as soft tissue abnormalities including meniscal degeneration, bursitis, tendonitis, Baker’s cyst and synovial inflammation; information about these soft tissue structures might provide more insight into their potential role in the complex process of pain in knee OA (Cook 2016). Musculoskeletal ultrasonography (US) is a relatively new imaging tool that is non-invasive, safe and relatively inexpensive and is able to create static as well as dynamic images. In addition, it has been shown to be more sensitive than clinical examination in picking up peri- and intra-articular soft tissue lesions (Bevers et al. 2014). Objectives To investigate the cause of pain in Knee OA by comparing sonographic and clinical findings in painful and non- painful osteoarthritic knee. Methods A cross-sectional case-control study carried out on fifty patients attending to Sohag University Hospitals rheumatology and rehabilitation outpatient clinic with Knee OA fulfilling ACR clinical criteria. They were divided into two groups. Group A (53) patients with knee pain (VAS 33 mm) during physical activity once at least in the previous 3 days prior to inclusion. Another (42) patients without knee pain for at least 1 month prior to inclusion (VAS 0 mm). All of the participants were subjected to the following: · Full history (demographic data and personal history, detailed history of general health condition and chronic or current diseases). · Knee clinical examination (including varus deformity angle assessment) · Sonographic evaluation: of Effusion, Synovial hypertrophy, Baker’s cyst, Enthesitis, Power Doppler by SOLAR score, menisci protrusion, bursitis, sonographic signs of Gout or CPPD and scoring of the osteophytes and cartilage Results Our study showed that the painful OA group are more obese, more varus deformities, effusion, synovial hypertrophy, cartilage changes, and higher grading of osteophytes than the control group. On the other hand, Baker cyst and meniscal protrusion echogenic foci, double contour, erosions, meniscal and cartilage calcification showed a non-significant difference between the two groups. We included all of the demographic, clinical and sonographic factors in a univariate regression analysis, and this analysis showed that synovial hypertrophy, effusion, the degree of cartilage changes, the degree of osteophytes, bursitis, and weight may be possible risk factors for pain among OA patients. Conclusions Cartilage degeneration, osteophytes, effusion, synovial hypertrophy, bursitis, and overweight respectively, are the leading causes of pain in knee OA.