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We performed 2 case-control studies among 108 patients with true coagulase-negative staphylococcal (CoNS) bacteremia diagnosed within 48 h of hospital admission. Seventy-nine patients (73%) with methicillin-resistant (MR) CoNS bacteremia and 29 patients (27%) with methicillin-susceptible (MS) CoNS bacteremia were compared with 79 randomly selected control patients without CoNS bacteremia. The presence of a central venous catheter was an independent risk factor for both MR- and MS-CoNS bacteremia (P <.001). Patients with MR-CoNS bacteremia were more frequently admitted from health care facilities (P =.02), more likely to have had previous MR Staphylococcus aureus infection or colonization (P =.02), and more likely to have received antibiotics in the previous 30 days (P =.02). The probability that bacteremia was caused by an MR strain, rather than an MS strain, was 62% among patients admitted from the community and 84% among patients admitted from health care facilities. This study identified epidemiological characteristics that can be used to distinguish between MR- and MS-CoNS bacteremia and found high rates of methicillin resistance among CoNS isolates recovered from patients admitted from the community, as well as from health care facilities.