The aim of this study was to investigate whether the pre- and postoperative plasma levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) were associated with outcome in colorectal cancer (CRC). Pre- and postoperative plasma TIMP-1 from 280 curatively resected CRC patients and carcinoembryonic antigen (CEA) in corresponding serum samples were measured and correlated with patient outcome (death, local recurrence (LR) and distant metastases (DM)). The results showed that the course of plasma TIMP-1 from pre- to postoperative levels correlated with patient outcome (P=0.005). However, postoperative plasma TIMP-1 alone was strongly associated with patient outcome, high TIMP-1 predicting short survival (P=0.002). Combining postoperative TIMP-1 and CEA demonstrated that high TIMP-1 and CEA levels predicted poor outcome (P<0.0001); multivariate analysis identifying both parameters as strong prognostic factors for survival, LR and DM (P<0.0001). In conclusion, postoperative plasma TIMP-1 predicts patient outcome both alone and in combination with CEA. Postoperative TIMP-1 may be a marker of residual disease after primary surgery for CRC.