Objective The epidemiology and outcomes of Multiple Organ Dysfunction Syndrome (MODS) are incompletely characterized in the pediatric population due to small sample size and conflicting diagnoses of organ failure. We sought to describe the epidemiology and outcomes of early MODS in a large clinical database of PICU patients based on consensus definitions of organ failure. Design Retrospective analysis of a contemporaneously collected clinical PICU database. Setting VPICU Performance System (VPS) database patient admissions from 1/2004-12/2005 for 35 US children’s hospitals. Patients We evaluated 63,285 consecutive PICU admissions from 1/2004-12/2005 in the VPS database. We excluded patients <1 month or >18 years of age, and hospitals with >10% missing values for MODS variables. We identified day 1 MODS by International Pediatric Sepsis Consensus Conference (IPSCC) criteria with day 1 laboratory and vital sign values. We evaluated functional status using Pediatric Overall Performance Category (POPC) and Pediatric Cerebral Performance Category (PCPC) scores from PICU admission and discharge. Interventions Analysis: Student’s t-test, Χ2, Mann-Whitney rank sum, Kruskal-Wallis, linear and logistic regression. Measurements and Main Results We analyzed 44,693 admissions from 28 hospitals meeting inclusion criteria. Overall PICU mortality was 2.8%. We identified day 1 MODS in 18.6% of admissions. Patients with day 1 MODS had higher mortality (10.0% v. 1.2%, p<0.001), longer PICU length of stay (3.6 v. 1.3 days, p<0.001) and larger change from baseline POPC and PCPC scores at time of PICU discharge (p<0.001). Infants had the highest incidence of day 1 MODS (25.2% vs. 16.5%, p<0.001) compared to other age groups. Conclusions Using the largest clinical dataset to date and consensus definitions for organ failure, we found that children with MODS present on day one of ICU admission have worse functional outcomes, higher mortality, and longer PICU length of stay than children who do not have MODS on day one. Infants are disproportionally affected by MODS.