We assessed the impact of personal protective equipment (PPE) doffing errors on healthcare worker (HCW) contamination with multidrug-resistant organisms (MDROs). Prospective, observational study. The study was conducted at 4 adult ICUs at 1 tertiary-care teaching hospital. HCWs who cared for patients on contact precautions for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci, or multidrug-resistant gram-negative bacilli were enrolled. Samples were collected from standardized areas of patient body, garb sites, and high-touch environmental surfaces in patient rooms. HCW hands, gloves, PPE, and equipment were sampled before and after patient interaction. Research personnel observed PPE doffing and coded errors based on CDC guidelines. We enrolled 125 HCWs; most were nurses (66.4%) or physicians (19.2%). During the study, 95 patients were on contact precautions for MRSA. Among 5,093 cultured sites (HCW, patient, environment), 652 (14.7%) yielded the target MDRO. Moreover, 45 HCWs (36%) were contaminated with the target MDRO after patient interactions, including 4 (3.2%) on hands and 38 (30.4%) on PPE. Overall, 49 HCWs (39.2%) made multiple doffing errors and were more likely to have contaminated clothes following a patient interaction (risk ratio [RR], 4.69; P = .04). All 4 HCWs with hand contamination made doffing errors. The risk of hand contamination was higher when gloves were removed before gowns during PPE doffing (RR, 11.76; P = .025). When caring for patients on CP for MDROs, HCWs appear to have differential risk for hand contamination based on their method of doffing PPE. An intervention as simple as reinforcing the preferred order of doffing may reduce HCW contamination with MDROs.