Objectives: The aim of this study is to assess the usefulness of prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) in monitoring of recurrent hepatocellular carcinoma (HCC) after curative resection. Methods: From April 2001 to March 2004, a total of 245 patients with histologically proven HCC and 267 non-HCC patients were recruited. Serial follow-up measurements of both alpha-fetoprotein (AFP) and PIVKA-II were performed in 27 patients who had recurrent HCC after resection. Results: In the initial HCC diagnosis, the sensitivity of AFP and PIVKA-II was 48.6% (119/245) and 75.1% (184/245), respectively, at the cutoff of 20 ng/ml for AFP and 40 mAU/ml for PIVKA-II (p < 0.01). The specificity was 81.3% (217/267) and 94.8% (253/267), respectively. When AFP and PIVKA-II were combined, the sensitivity and specificity was 83.3% (204/245) and 77.2% (206/267), respectively. In 27 patients developing recurrent HCC after curative surgical resection, the sensitivity of AFP and PIVKA-II was 40.7% (11/27) and 74.1% (20/27), respectively. Several fluctuating patterns of AFP and PIVKA-II were observed from initial diagnosis to recurrence. Conclusion: Our data suggest that PIVKA-II is a useful tumor marker for HCC, complementary to AFP. Serial measurements of both markers after resection might be helpful for early diagnosis of tumor recurrence.