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Contaminated hospital surfaces contribute significantly to the transmission of health care-associated infections. Although disinfectants reduce bioburden by up to 99%, bacterial growth can rebound within hours to precleaning levels. We tested the effectiveness of an innovative, long-acting water-stable organosilane (WSO) to achieve sustained decreases in bioburden on hard surfaces.A 5-month prospective, randomized, double-blind controlled study was performed. Eighteen intensive care unit rooms were randomly divided into placebo or treatment groups. Hard surfaces in all rooms were cleaned using the same protocol, except the placebo surfaces were cleaned with an inert saline solution and the treatment surfaces were treated with the WSO. Binomial regression with repeated measures were used to assess mean reductions in total bioburden as measured by colony forming units.The placebo resulted in average reductions in total colony forming units of 35% to 40% (relative risk reduction [RRR], 0.65; P < .01) and the WSO group averaged reductions of colony forming units by 66% to 99% (RRR, 0.55; P < .001). Total Staphylococcus aureus increased among the placebo rooms 30% (RRR, 0.69; P < .001), whereas in treatment rooms there was a reduction of 50%-60% (RRR, 0.57; P < .01). Although both sets of rooms saw reductions in bioburden or colony forming units, application of the WSO resulted in larger reductions. There was also greater variability in reductions in the placebo arm.This is the first randomized, double-blind controlled study of an innovative WSO on high-touch hard surfaces at risk for high bioburdens. Sustained reductions of bioburden with the monthly application of this unique WSO may be associated with significant reductions in the risk of health care-associated infections.