Religious fasting is associated with headache. This has been documented as "Yom Kippur Headache" and "First of Ramadan Headache." The Cox2 inhibitor, rofecoxib, has been reported effective in preventing perimenstrual migraine and in preventing recurrence of migraine. Given its 17 hour half-life, we undertook this study to see whether 50 mg rofecoxib taken just prior to the 25 hour Yom Kippur fast would be effective in preventing headache. We performed a double-blind randomized prospective trial of rofecoxib 50 mg versus placebo, taken just prior to the onset of fasting, Yom Kippur 2004. Healthy adults aged 18 to 65 were enrolled from the community and from hospital staff. Subjects completed a demographic data form and questions regarding headache history and a post-fast survey on headache during the fast, headache intensity, general ease of fasting, and side effects. We sent out 170 forms of which 105 were completed and returned. Of those subjects receiving rofecoxib (n = 53), 10 or 18.9% versus 34 or 65.4% of the placebo group (n = 52) had headache at some point during the fast (P < .0001). Severity of headache in the treatment group was significantly less for the treatment group (3.45 vs 6.29 on a visual analog scale of 10 (P= .009)). None of those receiving rofecoxib reported a "more difficult than usual fast" whereas the distribution of difficult to easy fast among the placebo group was more even. Rofecoxib 50 mg taken prior to a 25-hour ritual fast prevents and attenuates fasting headache.