To investigate whether institution of maximal sterile barrier precautions (SBPs) during arterial catheter (AC) insertion prevents catheter colonization, as is the case for central venous catheters (CVCs), a randomized study was conducted. Three hundred seventy-three patients in whom a radial or dorsalis pedis AC was going to be inserted were randomized to an SBP group or a standard-of-care group. These patients, in addition to all patients who were admitted to the unit with an AC already in place or who were not eligible for the randomized study, were observed for AC-related colonization and infection. Data for 272 randomized patients were available for analysis. The colonization incidence was 20.2 cases per 1000 catheter-days in the SBP group and 15.8 cases per 1000 catheter-days in the control group (P>.1). AC-related infection occurred in 3 patients in the SBP group and in 7 patients in the control group (P>.1). Five episodes of AC-related bloodstream infection were diagnosed (1.5 cases per 1000 catheter-days). Use of SBPs did not prevent AC colonization or infection. The incidence of AC-related infectious complications was comparable to the incidence of CVC-related infection reported in the literature.