353 patients with knee osteoarthritis (OA) were randomized to receive a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) daily, three capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400) daily or placebo. Over 3 months, the groups that received CS 1200 and CS 3*400 demonstrated greater improvement in pain and functioning than the placebo group. However, there was no significant difference in improvement between the CS 1200 and CS 3*400 groups. The three groups also did not differ with respect to patient compliance and rate of adverse events.