OBJECTIVE. Healthcare-acquired infections (HAIs) cause substantial patient morbidity and mortality. Items in the environment harbor microorganisms that may contribute to HAIs. Reduction in surface bioburden may be an effective strategy to reduce HAIs. The inherent biocidal properties of copper surfaces offer a theoretical advantage to conventional cleaning, as the effect is continuous rather than episodic. We sought to determine whether placement of copper alloy-surfaced objects in an intensive care unit (ICU) reduced the risk of HAI. DESIGN. Intention-to-treat randomized control trial between July 12, 2010, and June 14, 2011. SETTINg. The ICUs of 3 hospitals. PATIENTS. Patients presenting for admission to the ICU. METHODS. Patients were randomly placed in available rooms with or without copper alloy surfaces, and the rates of incident HAI and/or colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in each type of room were compared. RESULTS. The rate of HAI and/or MRSA or VRE colonization in ICU rooms with copper alloy surfaces was significantly lower than that in standard ICU rooms (0.071 vs 0.123; P = .020). For HAI only, the rate was reduced from 0.081 to 0.034 (P = .013). CONCLUSIONs. Patients cared for in ICU rooms with copper alloy surfaces had a significantly lower rate of incident HAI and/or colonization with MRSA or VRE than did patients treated in standard rooms. Additional studies are needed to determine the clinical effect of copper alloy surfaces in additional patient populations and settings.