Platelet-rich plasma (PRP) therapy has emerged as a potential treatment option for osteoarthritis (OA) due to its ability to promote tissue healing and anti-inflammatory effects. More evidences are needed to establish the optimal therapy protocol. We present here a retrospective analysis of 252 patients treated with PRP for big joints OA between 2020 and 2022. We aimed to evaluate the benefits of PRP combined with rehabilitation on pain and function as well as the potential prognosis factors. We observed clinically significant improvements in pain (VAS improvement 49% at 6 months, 45% at 12 months) and function (Single Assessment Numeric Evaluation i.e. SANE score improvement 44% at 6 months, 39% at 12 months). Multiple PRP shoots and high sports activity, especially competition level, were found as favorable prognosis factors. The authors would suggest offering systematically PRP therapy for competition sports practitioners. Moreover, authors suggest that multiple PRP shoots, spaced from 3 to 4 weeks, could be a viable treatment option for OA.