The purpose of the present study was to evaluate intra-articular ozone injection following arthroscopic surgery for knee osteoarthritis (OA) with regard to its efficacy in pain reduction, joint function and quality of life improvement. The present study retrospectively evaluated 80 patients with symptomatic knee OA (Kellgren-Lawrence grade II or III), who either did or did not receive 20 ml of 20 µg/ml ozone as an intra-articular injection after arthroscopic surgery. The minimum follow-up period was 12 months. The outcomes evaluated for knee OA were pain on the Visual Analogue Scale (VAS), Lequesne Index, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Clinical Global Impression (CGI). The VAS score in the ozone group was significantly better than that in the control group at all post-operative follow-up time-points (P<0.05). The ozone group also exhibited a significantly greater improvement in Lequesne Index scores (P<0.05). In the ozone group, the score on the WOMAC-pain, WOMAC-stiffness and WOMAC-function subscales, as well as the total WOMAC score decreased significantly (P<0.05). Furthermore, in the ozone group a significantly higher number of patients (P<0.05) with better CGI grades was encountered compared with that in the control group at the 12-month follow-up assessment, despite comparable baseline values in all aforementioned clinical measures between the two groups of patients. The present study suggests that intra-articular ozone injections after arthroscopic surgery may effectively improve the outcomes of arthroscopic surgery in terms of pain relief, functional improvement and quality of life in patients with knee OA of Kellgren-Lawrence grade II or III.