- Background: The authors describe a multifaceted cross-infection control program that was implemented to contain an epidemic of multidrug-resistant microorganisms (MRO) (carbapenem resistant Pseudomonas aeruginosa and Acinetobacter baumannii; extended spectrum β-lactamase producing Klebsiella pneumoniae, Escherichia coli, Enterobacter Cloacae, and Proteus mirabilis; and methicillin-resistant Staphylococcus aureus and Candida species). Objectives: To assess the effect of a control program on the incidence of cross-infection with MRO. Methods: Clinical criteria triaged patients into a high-risk wing (HRW) or a low-risk wing (LRW). Strict infection control measures were enforced; violations led to group discussions (not recorded). Frequent cultures were obtained, and use of antibiotics was limited. Each quarter, the incidence of MRO isolation was reported to all staff members. Results: Over a 6 year period, 1028 of 3113 patients were placed in the HRW. The incidence of MRO isolation within 48 hours of admission was 8.7% (HRW) vs. 1.91% (LRW) (P < 0.001). Acquired MRO infection density was 30.4 (HRW) vs. 15.6 (LRW) (P < 0.009). After the second year, the incidence of group discussions dropped from once or twice a month to once or twice a year. Conclusions: These measures contained epidemics. Clinical criteria successfully triaged HRW from LRW patients and reduced cross-infection between the medical center wings. The quarterly reports of culture data were associated with improved staff compliance. MRO epidemic control with limited resources is feasible.