While nausea often develops following exposure to trauma, little is known regarding the relationship between peri-traumatic nausea and prospective risk for developing posttraumatic stress disorder (PTSD). We examined the association between peri-traumatic nausea and PTSD symptom development in three independent cohorts. Participants were recruited from (1) the Emergency Departments (ED) at Grady Memorial Hospital (GMH) in Atlanta, GA, (2) from multiple other ED sites in the TRYUMPH Research Network, and (3) from the ED during evaluation for suspected acute coronary syndrome in the REACH cohort. Administration of IV ondansetron, the most predominant antiemetic used at GMH, was used as a surrogate marker for nausea in the initial GMH cohort; nausea was then directly assessed in the internal validation at GMH, and within the replication TRYUMPH Research Network and REACH cohorts. In the GMH cohort (N = 363), ondansetron administration was associated with increased 1- and 3-month posttrauma PTSD symptoms in adjusted models (all p's < 0.05). In the GMH internal validation, nausea significantly predicted 1 month (p = 0.009; n = 68) and 3 month (p = 0.029; n = 54) PTSD symptoms. In the TRYUMPH cohort (N = 1846), patient reported nausea in the ED was significantly associated with increased PTSD symptoms (p = 0.009) in adjusted models. In the REACH cohort (N = 758), peri-traumatic nausea was associated with PTSD symptom severity at the 1-month follow-up in adjusted models (p's ≤ 0.008). The current prospective data from three independent cohorts suggest that peri-traumatic nausea is a prospective predictor of PTSD symptom development. Further studies are needed to determine the mechanistic role of nausea as an intermediate phenotype of PTSD risk.