40 patients with knee osteoarthritis were randomized to three bi-weekly injections of either the low molecular weight fraction of 5% human serum albumin (LMWF-5A) or placebo. Patients were assessed for outcome related to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and incidence of adverse events. Reduction in WOMAC pain scores from 2 weeks to 12 weeks did not demonstrate a significant difference between groups. At 20 weeks, reduction was significantly greater in the LMWF-5A group compared to the placebo group, but effects at 24 weeks and 52 weeks were not reported. No serious treatment-related adverse events were noted in either group.