Background Vital signs are used in emergency care settings in the first assessment of children to identify those that need immediate attention. We aimed to develop and validate vital sign based Manchester Triage System (MTS) discriminators to improve triage of children at the emergency department. Methods and findings The TrIAGE project is a prospective observational study based on electronic health record data from five European EDs (Netherlands (n = 2), United Kingdom, Austria, and Portugal). In the current study, we included 117,438 consecutive children <16 years presenting to the ED during the study period (2012–2015). We derived new discriminators based on heart rate, respiratory rate, and/or capillary refill time for specific subgroups of MTS flowcharts. Moreover, we determined the optimal cut-off value for each vital sign. The main outcome measure was a previously developed 3-category reference standard (high, intermediate, low urgency) for the required urgency of care, based on mortality at the ED, immediate lifesaving interventions, disposition and resource use. We determined six new discriminators for children <1 year and ≥1 year: “Very abnormal respiratory rate”, “Abnormal heart rate”, and “Abnormal respiratory rate”, with optimal cut-offs, and specific subgroups of flowcharts. Application of the modified MTS reclassified 744 patients (2.5%). Sensitivity increased from 0.66 (95%CI 0.60–0.72) to 0.71 (0.66–0.75) for high urgency patients and from 0.67 (0.54–0.76) to 0.70 (0.58–0.80) for high and intermediate urgency patients. Specificity decreased from 0.90 (0.86–0.93) to 0.89 (0.85–0.92) for high and 0.66 (0.52–0.78) to 0.63 (0.50–0.75) for high and intermediate urgency patients. These differences were statistically significant. Overall performance improved (R² 0.199 versus 0.204). Conclusions Six new discriminators based on vital signs lead to a small but relevant increase in performance and should be implemented in the MTS.