Background <p>Moderate-to-severe knee osteoarthritis (KOA) involves progressive cartilage degeneration, meniscal tears, synovitis, and osteophyte formation, leading to persistent pain and functional impairment. Conventional therapies often provide inadequate relief. While platelet-rich plasma (PRP) injections have emerged as a promising regenerative treatment, their efficacy is predominantly established in mild-to-moderate KOA, with limited benefits observed in moderate-to-severe cases.</p> Case presentation <p>A 57-year-old Chinese male with bilateral moderate-to-severe knee osteoarthritis was treated with ultrasound-guided PRP injections. Over a 15-month period, he received a total of 34 bilateral intra-articular injections. At the final follow-up, both NRS and WOMAC scores were significantly reduced, concurrent with enhanced joint function and quality of life. Follow-up MRI revealed improvements in intra-articular structures, including the meniscal morphology, as well as a reduction in inflammation-related parameters, such as bone marrow edema, joint effusion, infrapatellar fat pad swelling, and synovitis.</p> Conclusions <p>This study concludes that ultrasound-guided long-term PRP injection is a safe and effective therapeutic strategy for moderate-to-severe knee osteoarthritis. It provides significant relief from pain, functional improvement, enhanced quality of life, and yields objective imaging evidence of joint improvement on MRI.</p>