Background: Contact Precautions are an infection control approach where patients with antibiotic resistant bacteria are isolated and disposable gloves and gowns are donned prior to room entry. Some studies suggest Contact Precautions may increase the occurrence of hospital adverse events. However, few studies have examined the effect of Contact Precautions on adverse events using a standard definition and accounting for the effect of severity of illness. We assessed whether Contact Precautions exposure was associated with patient adverse events in both ICU and non-ICU settings. Methods: The relationship between universal use of Contact Precautions (universal glove and gown use for all patient contact, regardless of colonization) and adverse events in the intensive care unit (ICU) was studied using medical record review of 1800 randomly sampled patients equally distributed over a 20 ICU cluster randomized trial. To reduce the influence of severity of illness, eligible patients could not be colonized or infected with antibiotic resistant bacteria. Within a non-ICU setting, a prospective cohort of 296 patients at the University of Maryland Medical Center (UMMC) matched on initial 3 day length of stay and admission location was used to study the association between usual use of Contact Precautions and adverse events. Results: The study of 1800 randomly selected patients from a cluster randomized trial of universal glove and gown use found that the rates of adverse events among patients in universal glove and gown ICUs were not statistically different (IRR, 0.91; 95% CI, 0.59-1.42; p=0.68). The UMMC prospective cohort observed significantly fewer noninfectious adverse events among patients exposed to traditional Contact Precautions compared to unexposed patients (IRR, 0.70; 95% CI, 0.51-0.95; p=0.02). Conclusions: In ICUs where healthcare workers donned gloves and gowns for all patient contact, patients were no more likely to experience adverse events than in control ICUs. In non-ICU settings Contact Precautions were associated with fewer noninfectious adverse events. Concerns about adverse events resulting from either universal glove and gown use or traditional use of Contact Precautions were not supported.