Background: Hypotension after major noncardiac surgery is associated with increased morbidity, mortality, and costs, and is often treated with postoperative vasopressor infusions. The frequency of administration in the postoperative period is unknown. Methods: This international prospective cohort study was conducted between October 2020 and October 2023. At each hospital, adults undergoing noncardiac surgery were enrolled into two cohorts: all consecutive patients for 1 week (Cohort A) and an additional sample of up to 30 consecutive patients administered postoperative vasopressor infusions within 1 yr (Cohort B). The primary outcome (Cohort A) was the incidence of postoperative vasopressor infusions, defined as any continuous infusion of vasopressors. Secondary outcomes included in-hospital mortality, organ dysfunction, length of hospital stay, and complications associated with postoperative vasopressor infusions (both cohorts). Results: In total, 25 675 participants were enrolled from 228 hospitals across 42 countries. In Cohort A, 770/19 768 (3.9%) participants received postoperative vasopressor infusions, with vasopressor use ranging between 0% and 18% across hospitals (median odds ratio: 2.30 [credible interval 1.96–2.73]). This variability did not alter after adjustment for case-mix and procedural characteristics. For both cohorts, postoperative vasopressor infusions were associated with higher (15.5%) in-hospital mortality, higher rates of organ failure, and longer hospital stay. Conclusions: Administration of postoperative vasopressors after noncardiac surgery varied across hospitals and was associated with worse outcomes. Variable practice across hospitals could not be explained by differences in case-mix. Clinical trial registration: https://clinicaltrials.gov/study/NCT03805230, ESAIC tracking ID: ESAIC_CTN_SQUEEZE.