Abstract Background: The peri-prosthetic joint infection (PJI) definition and diagnosis stay a challenge in orthopedic med-icine. It depends on different tools such as clinical, laboratory, and imaging assessments. Aim of Study: Is to highlight the role of the ultrasound (US) as a diagnostic tool for the evaluation and assessment of PJI in multiple joints to provide early management and care to the patients. Patients and Methods: This study included 70 adult patients with a prosthetic joint who were complaining of acute pain that was previously asymptomatic or persistent pain with no pain-free interval, and was evaluated by Greyscale ultra-sonography scan. The final clinical diagnosis of PJI in our study was reached by the established criteria of the American Musculoskeletal Infection Society. Results: Seventy patients were included in our study with the hips being the most affected joint. Joint effusion showed a sensitivity of 70.9%, specificity of 100%, and an overall diagnostic accuracy of 62.8% in the detection of PJI. Synovitis showed a sensitivity of 69%, specificity of 83.4%, and an overall diagnostic accuracy of 71.4% in the detection of PJI. Erosions and bone lesions showed a sensitivity of 50%, specificity of 50%, and an overall diagnostic accuracy of 50% in the detection of PJI. Soft tissue affection showed a sensitivity of 56.4%, specificity of 75%, and an overall diagnostic accuracy of 58.6% in the detection of PJI. Joint vascularity showed a sensitivity of 67.2%, specificity of 100%, and an overall diagnostic accuracy of 74.3% in the detection of PJI. Conclusion: The US could be used as an initial diagnostic tool for painful prosthesis evaluation before proceeding with more sophisticated and invasive procedures. As it is very sensitive in fluid detection and helps in the detection of extra-articular soft tissue lesions.