To investigate that a 6-month treatment with avocado soybean unsaponifiable (Piascledine 300 mg) once daily is as effective as with chondroitin sulfate 400 mg three times daily in femorotibial gonarthrosis, and also the carry-over effect for two more months is comparable. Patients were randomized (1:1) to the treatment groups. They received for 6 months 3 capsules chondroitin sulfate per day or one capsule of avocado soybean unsaponifiable (ASU) in a double-dummy technique. A 2-month post-treatment period followed to determine the carry-over effect. Primary efficacy criterion was the change of the WOMAC-index from study begin to end of treatment. Secondary criteria were the changes in Lequesne-index, pain on active movement and at rest, global assessment of efficacy. Three hundred sixty-four patients have been taken up into the trial. Three hundred sixty one patients were eligible for evaluation. One hundred eighty three received ASU 300 mg once daily, one hundred seventy eight chondroitin sulfate three times daily. The WOMAC-index decreased in both groups for approx. 50% to the end of therapy. During the post-treatment observation there was a further slight improvement. There was no statistical significant difference between the treatment groups during the entire observation. All other observed parameters showed the same pattern. The daily intake of rescue medication was reduced continuously. Overall efficacy has been rated excellent and good in more than 80% of the patients in both groups. Both drugs were safe and well tolerated. The first direct comparison between avocado soybean unsaponifiable 300 mg once daily and chondroitin sulfate three times daily reveiled no difference in efficacy or safety aspects between 1 capsule ASU 300 mg per day and 3 capsules chondroitin sulfate per day. It can be assumed that the once daily intake of ASU will lead to a better compliance in routine therapy.