Background Intraoperative hypotension is associated with increased morbidity and mortality. The Hypotension Prediction Index (HPI) is an advancement of the arterial waveform analysis to predict intraoperative hypotension minutes before episodes occur enabling preventive treatments. We tested the hypothesis that the HPI combined with a personalized treatment protocol reduces intraoperative hypotension when compared to arterial waveform analysis alone. Methods We conducted a retrospective analysis of 100 adult consecutive patients undergoing moderate‐ or high‐risk noncardiac surgery with invasive arterial pressure monitoring using either index guidance (HPI) or arterial waveform analysis (FloTrac) depending on availability (FloTrac, n = 50; HPI, n = 50). A personalized treatment protocol was applied in both groups. The primary endpoint was the incidence and duration of hypotensive events defined as MAP <65 mmHg evaluated by time‐weighted average of hypotension. Results In the FloTrac group, 42 patients (84%) experienced a hypotension while in the HPI group 26 patients (52%) were hypotensive (p = 0.001). The median (IQR) time‐weighted average of hypotension in the FloTrac group was 0.27 (0.42) mmHg versus 0.10 (0.19) mmHg in the HPI group (p = 0.001). Finally, the median duration of each hypotensive event (IQR) was 2.75 (2.40) min in the FloTrac group compared to 1.00 (2.06) min in the HPI group (p = 0.002). Conclusions The application of the HPI combined with a personalized treatment protocol can reduce incidence and duration of hypotension when compared to arterial waveform analysis alone. This study therefore provides further evidence of the transition from prediction to actual prevention of hypotension using HPI.