Background: Pleural infection is associated with a high morbidity and mortality. Development of a validated clinical risk score at presentation to identify those at high risk of dying would enable patient triage and may help formulate early management strategies. Methods: A clinical risk score was derived based on data from patients entering the multicenter UK pleural infection trial (first Multicenter Intrapleural Sepsis Trial [MIST1], n = 411). From 22 baseline clinical characteristics, model selection was undertaken to find variables predictive of poor clinical outcome. Outcomes were mortality at 3 months (primary), need for surgical intervention at 3 months, and time from randomization to discharge. The derived scoring system RAPID (renal, age, purulence, infection source, and dietary factors) was validated using patients enrolled in the subsequent MIST2 trial (n = 191). Results: Age, urea, albumin, hospital-acquired infection, and nonpurulence predicted poor outcome. Patients were stratified into low-risk (0-2), medium-risk (3-4), and high-risk (5-7) groups. Using the low-risk group as a reference, a RAPID score of 3 to 4 and . 4 was associated with an OR of 24.4 (95% CI, 3.1-186.7; P = .002) and 192.4 (95% CI, 25.0-1480.4; P < .001), respectively, for death at 3 months. In the validation cohort (MIST2), a medium-risk RAPID score was nonsignifi- cantly associated with mortality (OR, 3.2; 95% CI, 0.8-13.2; P = .11), and a high-risk score was associated with increased mortality (OR, 14.1; 95% CI, 3.5-56.8; P < .001). Hospitalization duration was associated with increasing RAPID score (score 0-2: median duration = 7, interquartile range 6-13; score . 5: median duration = 15, interquartile range 9-28, P = .08). Conclusions: The RAPID score may permit risk stratification of patients with pleural infection at presentation. © 2014 American College of Chest Physicians.