In the setting of closed long bone fractures, the pooled results failed to demonstrate superiority of multiple-dose prophylaxis over a single-dose strategy. The pooled estimates suggest that surgical wound infections are relatively rare events and that any potential difference in infection rates between prophylaxis strategies is likely quite small. However, because the confidence interval surrounding the pooled risk ratio spans 1.0 by such a large amount, we are unable to definitively recommend a preferred dosing regimen to prevent surgical wound infections. Although future research is required to ensure our prophylaxis decisions continue to be evidence based and cost-effective, it is unlikely that a single clinical trial will be able to provide the answer. The use of other quantitative methods, such as cost-effectiveness analysis, may be helpful in modeling an optimal prophylaxis strategy.