The efficacy of the combination of dihydroergotamine (10 mg) with acetylsalicylic acid (80 mg) (DHE + ASA) in the prophylaxis of migraine was studied in a double-blind, placebo-controlled crossover trial (8 weeks twice). Of 45 patients who entered the study, 38 completed it. The number of attacks was significantly (p = 0.003) reduced during active treatment (11.5 ± 6.2) compared with placebo (16.6 ± 9.9). The mean duration, the mean severity, and the mean score for symptomatic acute medication of attacks did not differ significantly. The overall assessment made by the patients themselves was in favor of DHE + ASA (p = 0.001). These results indicate a moderately beneficial effect of the dihydroergotamine/low-dose acetylsalicylic acid combination in migraine prophylaxis.