Introduction Several single-center studies and meta-analyses have shown that perioperative goal-directed therapy may significantly improve outcomes in general surgical patients. We hypothesized that using a treatment algorithm based on pulse pressure variation, cardiac index trending by radial artery pulse contour analysis, and mean arterial pressure in a study group, would result in reduced complications, reduced length of hospital stay and quicker return of bowel movement postoperatively in abdominal surgical patients, when compared to a control group. Methods 160 patients undergoing elective major abdominal surgery were randomized to the Study Group (79 patients) or to the Control Group (81 patients). In the Study Group hemodynamic therapy was guided by pulse pressure variation, cardiac index trending and mean arterial pressure. In the Control Group hemodynamic therapy was performed at the discretion of the treating anesthesiologist. Outcome data were recorded up to 28 days postoperatively. Results The total number of complications was significantly lower in the Study Group (72 vs. 52 complications, p = 0.038). In particular, infectious complications were significantly reduced (Study Group: 13 vs. Control Group: 26 complications, p = 0.023). There were no significant differences between the two groups for return of bowel movement (Study Group: 3 vs. Control Group: 2 days postoperatively, p = 0.316), duration of post anesthesia care unit stay (Study Group: 180 vs. Control Group: 180 minutes, p = 0.516) or length of hospital stay (Study Group: 11 vs. Control Group: 10 days, p = 0.929). Conclusions This multi-center study demonstrates that hemodynamic goal-directed therapy using pulse pressure variation, cardiac index trending and mean arterial pressure as the key parameters leads to a decrease in postoperative complications in patients undergoing major abdominal surgery.