This study is a retrospective work of ambulatorial injections in patients suffering from Class II osteoarthritis (OA) of the knee. The research was conducted from January 2012 to July 2012 in a private clinic in Benevento, Hospital Val D’Elsa, Poggibonsi, Siena. A total of 60 patients were treated with intraarticular knee injections. Group A, composed of 30 patients (15 male and 15 female), was treated with injections of low molecular weight Hyaluronic Acid and Group B, composed of 30 patients (15 male and 15 female) was treated with injections of Ploynucleotide. At the six month follow-up, Group B showed a statistically significant difference (p<0.05) of the Visual Analogue Scale (VAS); the Knee injury and Osteoarthritis Outcome Score for Group B also showed a statistically significant difference (p<0.05). The results obtained suggest that polynucleotides can be considered as a valid alternative to hyaluronic acid for the treatment of symptomatic osteoarthritis of the knee.