191 patients with knee osteoarthritis were randomized to oral supplementation with either undenatured type II collagen (UC-II), glucosamine hydrochloride plus chonndroitin sulfate (GC), or a placebo. The purpose of this study was to determine the efficacy of UC-II compared to GC or placebo in symptomatic management of mild-to-moderate knee osteoarthritis. Patient-reported outcome measures of the Western Ontario and McMaster Universities Osteoarthritis Index, a visual analog scale for pain, and the Lequesne Functional Index were assessed over 180 days of treatment. Results demonstrated significantly greater improvement from baseline to 180 days in all three outcome measures following treatment with UC-II versus either GC or placebo.