Objective Intraoperative arterial hypotension (IOH) is associated with poor patient outcome. This study aims to compare the hemodynamic effects of Cafedrine/Theodrenaline (C/T) and Noradrenaline (NA) for the treatment of hypotension in patients who develop IOH after anesthesia induction. Research design and methods This is a national, randomized, parallel-group, multicenter, and open-label study. Adult patients (≥50 years, ASA-classification III–IV) who undergo elective surgery will be included. When IOH (MAP <70 mmHg) develops, C/T or NA will be given as a bolus injection (“bolus phase”, 0–20 min after initial application) and subsequently as continuous infusion (“infusion phase”, 21–40 min after initial application) to achieve MAP = 90 mmHg. Hemodynamic data are captured in real time by advanced hemodynamic monitoring. Results Primary endpoints, i.e. the treatment-related difference in average mean arterial pressure (MAP) during the “infusion phase” and the treatment-related difference in average cardiac index during the “bolus phase” are assessed (fixed-sequence method). Non-inferiority of C/T compared to NA in achieving 90 mmHg (MAP) when applied as continuous infusion is hypothesized. In addition, superiority of C/T over NA, applied as bolus injection, in increasing cardiac index is postulated. It is estimated that 172 patients are required to establish statistical significance with a power of 90%. After adjusting for ineligibility and dropout rate, 220 patients will be screened. Conclusion This clinical trial will yield evidence for marketing authorization of C/T applied as continuous infusion. Additionally, the effects of C/T compared to NA on cardiac index will be assessed. First results of the “HERO”-study are expected in 2024. DRKS identifier: DRKS00028589. EudraCT identifier: 2021-001954-76.