Between January 1956 and July 1981, 40 patients with Klippel-Trenaunay syndrome were seen at the Mayo Clinic. Twenty male and 20 female patients presented with the classic triad of soft tissue and bony hypertrophy of the extremity, hemangioma, and varicosity without evidence of functional arteriovenous fistulae. The lower extremity was involved in 38 patients (95%), the upper extremity in six patients (15%). In four of these cases (10%), both the upper and lower extremities were affected. The disease was unilateral in 34 patients (85%), bilateral in five cases (12.5%), and crossed-bilateral in one case (2.5%). Surgery was done in 13 patients (32.5%), nine of whom were operated on at the Mayo Clinic and four of whom had had previous surgery elsewhere. Excision and stripping of varices were performed in three patients; of these three, a deterioration of symptoms was observed in one, but the procedure was beneficial in the other two. Partial varicectomy was performed in four cases, while resection of the angioma was attempted in eight cases, with good results in three cases of small angiomas. Femoral and tibial epiphysiodesis stopped the overgrowth and produced an excellent result in one case. In four cases of epiphysiodesis at the foot level and two cases of derotational tibial osteotomy, moderate improvement was achieved. The indication for vascular or orthopedic surgery should be carefully considered in each patient who has this syndrome. One patient (2.5%) died of a severe form of the disease, but the relatively benign course is documented by the 21 patients (52.5%) who are free of complaints without any treatment or with elastic support only.