Currently, there is no consensus in the literature regarding which patients with calf vein thrombi are at high risk for proximal propagation. This study examined patients with isolated calf vein thrombi with serial duplex scans in order to identify risk factors that would predict outcome. Between May 1989 and November 1994, 288 patients were identified with isolated calf vein thrombi. One hundred ninety-two of them had sequential scans performed. Fifty-three (28%) of the 192 patients had propagation of their initial thrombi. The most proximal level of propagation was the popliteal vein in 11 patients, the superficial femoral vein in 5, the common femoral vein in 5, adjacent tibial or soleal veins in 24, adjacent soleal veins alone in 7, and the lesser saphenous vein in 1. Three patients whose thrombi propagated had free-floating thrombus tips in the large veins of their thighs. Symptoms, prophylaxis, and risk factor analysis comparing those patients whose thrombi propagated to those whose thrombi did not found no statistically significant prognostic value. Single or multiple calf vein thrombi did not predict propagation. Of the 23 patients treated with heparin, only 3 had thrombus propagation. None of these reached the level of the knee (including popliteal vein). The natural history of distal lower extremity thrombosis does not appear to be as benign as previously believed.