The purpose of the present investigation was to examine the effects of 30 days of treatment with a topical cream consisting of cetylated fatty acids on static postural stability and plantar pressures in patients with osteoarthritis (OA) of one or both knees. Forty patients diagnosed with knee OA were randomly assigned to 1 of 2 topical treatment groups: (a) cetylated fatty acid (CFA; N = 20; age = 62.7 +/- 11.7 years); or (b) placebo (P; N = 20; age = 64.6 +/- 10.5 years). Patients were tested on 2 occasions: (a) baseline (T1), and (b) following a 30-day treatment period consisting of cream application twice per day (T2). Assessments included 20- and 40-second quiet standing protocols on a force plate to measure center of pressure (COP) total excursion length, COP velocity, and rearfoot and forefoot plantar pressure distribution. In the CFA group, a significant reduction in the COP excursion length and velocity were observed at T2, whereas no significant differences were observed in the P group. No significant differences in mean forefoot, rearfoot, or rearfoot-to-forefoot plantar pressure ratios were observed in either group at T2. However, in a subgroup of participants designated to be right- or left-side dominant, improvements in the right-to-left forefoot plantar pressure ratios were observed in both groups. These data indicate that 30 days of treatment with a topical cream consisting of cetylated fatty acids improves static postural stability in patients with knee OA presumably due to pain relief during quiet standing. Such over-the-counter treatment may help improve the exercise trainability of people with OA.