Hemodynamic and depth of anesthesia (DOA) monitoring are used in many high-risk surgical patients without well-defined indications and objectives. We implemented monitoring guidelines to rationalize hemodynamic and anesthesia management during major cancer surgery. In early 2014, we developed guidelines with specific targets (Mean arterial pressure > 65 mmHg, stroke volume variation < 12%, cardiac index > 2.5 l min-1 m-2, central venous oxygen saturation > 70%, 40 < bispectral index < 60) for open abdominal cancer surgeries > 2 h. Pre-, intra-, and post-operative data were collected from our electronic medical record database and compared before (March-August 2013) and after (March-August 2014) guideline implementation. A total of 596 patients were studied, 313 before (Before group) and 283 after (After group) guideline implementation. The two groups were comparable for age, ASA score, physiological P-POSSUM score, and surgery duration, but the operative P-POSSUM score was higher in the after group (20 vs. 18, p = 0.009). The use of cardiac output, central venous oxygen saturation and DOA monitoring increased from 40 to 61%, 20 to 29%, and 60 to 88%, respectively (all p-values < 0.05). Intraoperative fluid volumes decreased (16.0 vs. 14.5 ml kg-1 h-1, p = 0.002), whereas the use of inotropes increased (6 vs. 11%, p = 0.022). Postoperative delirium (16 vs. 8%, p = 0.005), urinary tract infections (6 vs. 2%, p = 0.012) and median hospital length of stay (9.6 vs. 8.8 days, p = 0.032) decreased. In patients undergoing major open abdominal surgery for cancer, despite an increase in surgical risk, the implementation of guidelines with predefined targets for hemodynamic and DOA monitoring was associated with a significant improvement in postoperative outcome.