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Distinguishing between primary and secondary headaches (HAs) is essential for the safe and effective management of patients with HA. A favorable response to analgesics may be observed with both classes of HAs and therefore is not a good predictor of who needs further evaluation.To systematically review the data that a favorable response to analgesics including triptans should not be used to exclude a serious secondary cause of HA.PubMed search of English-language articles between 1980 and 2007 and reference lists of these articles. Two authors independently reviewed articles for study results and quality. Inclusion was based on 100% agreement between authors. We included articles that described secondary HAs as (1) having a favorable response to analgesics and/or (2) having a favorable response to sumatriptan. Of the 548 studies identified by our search strategy, 18 were included in our final analysis.Seven of the 18 studies found that 46/103 patients (44%) described a significant or complete resolution of secondary HA from medications such as anti-emetics and nonsteroidal anti-inflammatory drugs (NSAIDs). Eleven of the 18 articles including 25/25 patients (100%) described a significant or complete resolution of secondary HA from sumatriptan, a serotonin 5HT agonist.A favorable response to analgesics including triptans should not be used to exclude a serious secondary cause of HA.