To determine the roles of "colonization pressure," work load or patient severity in patient acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs). Prospectively collected data from October 1996 through December 1998. A 12-bed medical ICU in a university-affiliated general hospital. Patients with risk factors for MRSA admitted to the ICU were screened within 72 hours of admission and weekly thereafter. MRSA was considered imported if detected during the first 72 hours of admission and nosocomial if detected only thereafter. Three screening strategies were used on admission during three consecutive periods. The unit of time chosen for measurements was the week. Weekly colonization pressure (WCP) was defined as the number of MRSA-carrier patient-days/total number of patient-days. Patient severity (number of deaths, Simplified Acute Physiologic Score SAPS II), work load (number of admis sions, Omega score), and colonization pressure (number of MRSA carriers at the time of admission, WCP) were compared with the number of MRSA-nosocomial cases during the following week. Of the 1,016 patients admitted over 116 weeks, 691 (68%) were screened. MRSA was imported in 91 (8.9%) admitted patients (13.1% of screened patients) and nosocomial in 46 (4.5%). The number of MRSA-nosocomial cases was correlated to the SAPS II (P=.007), the Omega 3 score (P=.007), the number of MRSA-imported cases (P=.01), WCP (P<.0001), and the screening period (P<.0001). In multivariate analysis, WCP was the only independent predictive factor for MRSA acquisition (P=.0002). Above 30% of WCP, the risk of acquisition of MRSA was approximately fivefold times higher (relative risk, 4.9; 95% confidence interval, 1.2-19.9; P<.0001). Acquisition of MRSA in ICU patients is strongly and independently influenced by colonization pressure.