23 patients with mild-moderate knee osteoarthritis were randomized to three weekly intra-articular injections of either hyaluronic acid (HA; Synvisc Hylan G-F 20) or photo-activated platelet-rich plasma (PRP). The purpose of this study was to compare pain and functional outcome between the two groups at 4 and 12 week follow-up after the last injection. Efficacy outcomes included a visual analog scale (VAS) for pain, the Knee Injury and Osteoarthritis Outcome Scale (KOOS), the Knee Quality of Life 26-Item questionnaire (KQoL-26), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and functional performance tests. Findings demonstrated no significant differences between groups at either 4 or 12 week follow-up for any outcome measures. Nonetheless, as this was a pilot study, the trial was underpowered to accurately assess comparative efficacy between treatment options.