Osteoarthritis of the knee is a common condition that can cause considerable pain and disability. Various forms of lateral wedging may be effective in the treatment of medial compartment osteoarthritis, but it is not known whether incorporating a lateral wedge into a custom-molded foot orthosis will achieve similar results. Therefore, 30 subjects (21 men and 9 women) aged 29 to 77 years (mean +/- SD, 58.1 +/- 11.6 years) with radiographically confirmed medial compartment knee osteoarthritis were issued custom-molded foot orthoses with a 5 degrees lateral heel wedge. Pain levels were recorded using a 100-mm visual analog pain scale on the date of issue of the orthoses (baseline) and again 3 and 6 weeks later. Mean +/- SD pain levels were significantly reduced at 3 weeks (34 +/- 22 mm) and 6 weeks (23 +/- 22 mm) versus baseline (69 +/- 19 mm) (F2 = 39.57). The degree of pain reduction was greater in patients with less severe osteoarthritis. At 6 weeks, all subjects had achieved at least some reduction in pain, and 28 reported that their orthoses were comfortable. This preliminary study indicates that laterally wedged foot orthoses may be beneficial in the treatment of mild-to-moderate osteoarthritis of the medial compartment of the knee. Further investigations using a larger sample, longer follow-up, and a no-treatment control group seem warranted.