Isposition, insult, response, and organ dysfunction (PIRO) concept of sepsis can be used to predict the risk of unplanned ICU transfer after ED admission. Methods: The ICU transfer group included 313 patients with unplanned transfer to the ICU within 48 hours of ED admission, and the control (non-transfer) group included 736 randomly sampled patients who were not transferred to the ICU. Two-thirds of the total 1049 patients in this study were randomly assigned to a derivation group, which was used to develop the PIRO model, and the remaining patients were assigned to a validation group. Results: Independent predictors of deterioration within 48 hours after ED admission were identified by the PIRO concept. PIRO scores were higher in the ICU transfer group than in the non-transfer group, both in the derivation group [median (mean ± SD), 5 (5.7 ± 3.7) vs. 2 (2.5 ± 2.5); p < 0.001], and in the validation group [median (mean ± SD), 6 (6.0 ± 3.4) vs. 2 (2.4 ± 2.6); p < 0.001]. The proportion of ICU transfer patients with a PIRO score of 0–3, 4–6, 7–9, and ≥10 was 14.1%, 46.5%, 57.3%, and 83.8% in the derivation group (p < 0.001) and 12.8%, 37.3%, 68.2%, and 70.0% in the validation group (p < 0.001), respectively. The proportion of inpatient mortality in patients with a PIRO score of 0–3, 4–6, 7–9, and ≥10 was 2.6%, 10.1%, 23.2%, and 45.9% in the derivation group (p < 0.001) and 3.3%, 12.0%, 18.2%, and 20.5% in the validation group (p < 0.001), respectively. Conclusion: The PIRO concept of sepsis may be used in undifferentiated medical ED patients as a prediction system for unplanned ICU transfer after admission....