Background: Knee osteoarthritis is severe progressive and most commonly diagnosed articular disease and its incidence is increasing around the world depending on age. This pathologic condition which limits daily activity of patients can be characterized by degeneration of cartilage and inflammation. Although non-steroidal anti-inflammatory (NSAII) agents and other analgesics are routinely used treatment options, the potential effects of intraarticular injections including hyaluronic acid (HA) have also been demonstrated by various studies. However, few studies compare the efficacy of a single high molecular weight (HMW) high dose and a triple HMW low dose. This study aimed to compare the efficacy of single high molecular weight (HMW) high dose (2 mL / 60 mg) and triple HMW low dose (2 mL /30 mg) intra-articular injection of HA in knee osteoarthritis (OA) patients by evaluating function and pain parameters during 12 months. Methods: This is a single-center, retrospective clinical study that included and involved 128 patients. Group I (n=64) patients received triple 30 mg HA injections (SEMICAL®) with one-week intervals, while Group II (n=64) patients received a single 60 mg HA injection (SEMICAL®). Lequesne Index, WOMAC and VAS scores were recorded to assess pain and function during a 12-month period. Results: There was no significant difference in characteristics of patient demographics. Our finding indicate that WOMAC, VAS score, and Lequesne Index values during follow-up visits exhibited a decrease, signifying improvement in the clinical condition. Notably, scores were significantly more favorable with the 30 mg of HA injection compared to the 60 mg of HA injection. Conclusion: This study suggests that the triple low-dose injection of HMW HA is more effective in improving WOMAC, VAS scores and Lequesne Index values than a single high-dose injection.