Because patients with cyclic vomiting often (82%) have a family history of migraines and often (60%) respond to antimigraine therapy, we investigated whether an initial therapeutic trial could precede diagnostic testing. We used a decision analysis program to compare the cost and benefit of three initial treatment strategies. The costs of the three strategies were extensive diagnostic evaluation, $3020; empiric treatment alone, $1830, and upper GI series with small-bowel follow-through (UGI-SBFT) plus empiric treatment, $1600, respectively. When compared with the extensive evaluation strategy, initial antimigraine treatment avoided 65% of the esophagogastroduodenoscopys. On the basis of this decision analysis, a UGI-SBFT plus empiric migraine therapy was the most cost-effective initial strategy to treat cyclic vomiting syndrome. The cost of complications of a missed malrotation with volvulus was higher than that of adding a UGI-SBFT to each evaluation.