A systematic review was performed to determine the effectiveness of different approaches for eradicating methicillin-resistant Staphylococcus aureus carriage. Twenty-three clinical trials were selected that evaluated oral antibiotics (7 trials), topically applied antibiotics (12 trials), or both (4 trials). Because of clinical heterogeneity, quantitative analysis of all studies was deemed to be inappropriate, and exploratory subgroup analyses were performed for studies with similar study populations, methods, and targeted bacteria. The estimated pooled relative risk of treatment failure 1 week after short-term nasal mupirocin treatment, compared with placebo, was 0.10 (range, 0.07-0.14). There was low heterogeneity between study outcomes, and effects were similar for patients and healthy subjects, as well as in studies that included only methicillin-susceptible S. aureus carriers or both methicillin-susceptible S. aureus and methicillin-resistant S. aureus carriers. The development of drug resistance during treatment was reported in 1% and 9% of patients receiving mupirocin and oral antibiotics, respectively. Short-term nasal application of mupirocin is the most effective treatment for eradicating methicillin-resistant S. aureus carriage, with an estimated success of rate of 90% 1 week after treatment and approximately 60% after a longer follow-up period.