Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 can predict cancer mortality, including colorectal cancer (CRC) mortality, in type 2 diabetic subjects. However, it remains unknown if serum VAP-1 can predict mortality in CRC patients. This prospective cohort study investigates if serum VAP-1 is a novel biomarker for mortality prediction in CRC.We enrolled 300 CRC patients. Preoperative serum VAP-1 was measured by time-resolved immunofluorometric assay. They were followed until September 2009 or death, which was ascertained by the National Death Registration System.The median follow-up period was 4.7 years. Compared with normal counterpart, VAP-1 immunoactivity was upregulated in CRC tissues, especially at the invasion front. Serum VAP-1 can independently predict all-cause mortality (HR: 1.0026, 95% CI: 1.0003-1.0050, P5 ng/ml, tumor grading, tumor staging, and serum VAP-1 could stratify CRC patients into low-, intermediate-, and high-risk subgroups, with a 5-year mortality rate of 10%, 34%, and 78%, respectively.Serum VAP-1 predicts mortality independently and improves risk stratification in CRC subjects.