We describe a model to examine the cost-effectiveness of various laboratory-screening approaches to detect methicillin-resistant Staphylococcus aureus (MRSA). A critical literature review was used to derive relevant data on the sensitivity (X), specificity (S) and time to result (T) of different tests. Additional cost information was provided by a hospital. Tests were considered in four interactive groups based on a hierarchy of procedures used in laboratories. X, S and Ts of screening tests were then used in formulae to calculate effectiveness for the various tests. The model was developed to explore the effects on MRSA infection acquisition of differing X, S and T for the different tests in detecting MRSA colonized patients admitted to a high-risk unit such as an intensive care unit. It was concluded that taking a sample from the nose alone and inoculating directly on to Ciprofloxacin Baird-Parker agar without broth incubation and confirmation by a Pastorex Staph-Plus test without any methicillin resistance confirmation test was the most cost-effective approach. The complexity of designing this apparently simple scenario is apparent, and we describe many other factors that would need to be considered to refine this model further. However, this and other models should aid the debate and development of more cost-effective screening strategies given the lack of standardization or agreement concerning so many of the variables within the UK and elsewhere.