Background: Patients undergoing major surgery are at risk of complications, so-called serious adverse events (SAE). Continuous monitoring may detect deteriorating patients by recording abnormal vital signs. We aimed to assess the association between abnormal vital signs inspired by Early Warning Score thresholds and subsequent SAEs in patients undergoing major abdominal surgery. Methods: Prospective observational cohort study continuously monitoring heart rate, respiratory rate, peripheral oxygen saturation, and blood pressure for up to 96 h in 500 postoperative patients admitted to the general ward. Exposure variables were vital sign abnormalities, primary outcome was any serious adverse event occurring within 30 postoperative days. The primary analysis investigated the association between exposure variables per 24 h and subsequent serious adverse events. Results: Serious adverse events occurred in 37% of patients, with 38% occurring during monitoring. Among patients with SAE during monitoring, the median duration of vital sign abnormalities was 272 min (IQR 110–447), compared to 259 min (IQR 153–394) in patients with SAE after monitoring and 261 min (IQR 132–468) in the patients without any SAE (p =.62 for all three group comparisons). Episodes of heart rate ≥110 bpm occurred in 16%, 7.1%, and 3.9% of patients in the time before SAE during monitoring, after monitoring, and without SAE, respectively (p <.002). Patients with SAE after monitoring experienced more episodes of hypotension ≤90 mm Hg/24 h (p =.001). Conclusion: Overall duration of vital sign abnormalities at current thresholds were not significantly associated with subsequent serious adverse events, but more patients with tachycardia and hypotension had subsequent serious adverse events. Trial registration: Clinicaltrials.gov, identifier NCT03491137.