The high rate of recurrence after surgical resection of hepatocellular carcinoma (HCC) is a major therapeutic challenge. Postoperative injection of 131-iodine-labeled lipiodol (131I-Lip) into the hepatic artery has been proposed as adjuvant treatment (Lau et al.). We analyzed 2 retrospective series of matched patients treated in our unit before and after addition of 131I-Lip adjuvant therapy to our standard surgical strategy. Thirty-eight patients who had undergone surgical resection of HCC after January 1999 were given adjuvant intra-arterial injection of 131I-Lip after surgery. These patients were matched with 38 other patients who had undergone surgical resection only between January 1997 and January 1999. The frequency of recurrences, disease-free rates, and overall survival rates were compared. The 2 groups were similar for clinical, biologic, or histologic parameters studied and Cancer Liver Italian Program scores. There were 15 recurrences in the group without adjuvant treatment and 9 in the group with 131I-Lip adjuvant treatment. The 1-, 2-, and 3-year disease-free survival rates (±95% confidence interval) were different (P < .02): 94.7% ± 3.6%, 83.7% ± 6.1%, and 68.4% ± 9.7%, respectively, in the 131I-Lip group versus 73.7% ± 7.1%, 54.3% ± 8.2%, and 41.5% ± 10.5% in the surgery group. The 1-, 2-, and 3-year survival rates (±95% confidence interval) also were different (P < .02): 94.7% ± 3.6%, 91.7% ± 4.6%, and 91.7% ± 4.6%, respectively, in the 131I-Lip group versus 94.7% ± 3.6%, 71.3% ± 7.8%, and 49.9% ± 10% in the surgery group. In conclusion, this retrospective analysis supports the promising contribution of postoperative injection of 131I-Lip after resection of HCC. A randomized study including more patients would be necessary to confirm its contribution to therapeutic management.