Background: Precision medicine approaches targeting patients based on disease subtype have transformed approaches to cancer, asthma, and other heterogeneous syndromes. Two distinct subphenotypes of ARDS have been identified in three US-based clinical trials and respond differently to positive end-expiratory pressure and fluid management. It remains unknown if these subphenotypes exist in different populations and respond differently to pharmacotherapies. Methods: We conducted a secondary analysis using data from 539 patients enrolled in a UK multicenter, placebo-controlled randomized trial of simvastatin for ARDS (HARP-2). Latent class analysis was applied to baseline data without consideration of outcomes to identify subphenotypes. Clinical outcomes were compared across subphenotypes and treatment groups. Findings: A two class (two-subphenotype) model was an improvement over a one class model (pInterpretation: Two subphenotypes of ARDS were identified in the HARP-2 cohort, withdistinct clinical and biological features and disparate clinical outcomes; the hyper-inflammatory subphenotype had improved survival with simvastatin compared to placebo. These findings support further pursuit of predictive enrichment strategies in critical care clinical trials.