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Clinicians often consider ibuprofen to be more effective than acetaminophen for the treatment of headaches. This impression is reinforced by practice parameters or guidelines that either consider acetaminophen to be less effective or attribute less evidence to its efficacy when compared with ibuprofen. 1–4 When these medications are compared head-to-head in a randomized controlled trial (RCT), little evidence exists that demonstrates the superiority of one over the other. The objective of this article was to review the evidence supporting the concept that ibuprofen is superior to acetaminophen for the treatment of benign headaches, by reviewing the RCTs offering a direct comparison.