PurposeThe purpose of this study was to evaluate the impact of gender on the efficacy of platelet‐rich plasma (PRP) in patients with knee osteoarthritis (KOA), comparing their short‐term response between men and women.MethodsFour hundred‐eighteen patients (529 knees) were included. Patients were treated with three injections of PRP on a weekly basis. Blood and PRP samples were randomly tested. Patients were asked to complete the knee injury and osteoarthritis outcome score (KOOS) and 12‐item short form survey (SF‐12), at baseline and 6 months. Success rates were calculated according to a reduction in the pain score of at least 9.3 points [minimal clinically important improvement (MCII)]. Comparative tests and multivariate regression were performed.ResultsThe PRP had a platelet concentration factor of 2.0X compared to blood levels, with no leucocytes or erythrocytes. KOOS scores showed an increase from baseline to 6 months (p < 0.0001). There was an increase in the physical component summary (PCS) (p < 0.0001) and mental component summary (MCS) (p < 0.01) of the SF‐12. The number of knees of women with MCII was 156 out of 262 (59.6%), whereas the number of knees of men was 136 out of 267 (50.9%) (p = 0.0468). Women had worse baseline scores on pain (p = 0.009), PCS (p < 0.0001) and MCS (p < 0.0001).ConclusionAlthough the symptomatology generated by KOA was worse in women when compared to men, treatment with repeated injections of PRP was effective, ultimately achieving a higher improvement in women providing comparable final follow‐up outcomes between men and women.Level of EvidenceLevel IV