Drug-induced headache, particularly ergotamine-induced headache, is a common problem in migraine treatment. Some case reports suggest that even the new serotonergic antimigraine drugs such as sumatriptan can lead to overuse and subsequent drug-induced headache. We performed a controlled study to identify the rate of sumatriptan overuse and sumatriptan-induced headache and compared it to the rate of ergotamine overuse and ergotamine-induced headache. Two thousand sixty-five consecutive heachache patients, all experienced in intake of sumatriptan (n = 631) or ergotamine (n = 620), were enrolled over a three-year study period. The rates of overuse and drug-induced headache and the clinical features of the subgroups were compared. Risk factors for sumatriptan overuse were identified. The rates of ergotamine and sumatriptan overuse were 14.2% and 3.5%, respectively (p < 0.001). Drug-induced headache could be found more frequently in cases of ergotamine overuse than in cases of sumatriptan overuse (68% versus 32%; p < 0.01). Development of sumatriptan overuse was most common in patients with previous drug-induced headache (68%), combined headache as the primary headache type (45%), and subcutaneous application of sumatriptan (45%). We conclude that sumatriptan intake can lead to overuse and subsequent drug-induced headache. The risk for overuse and drug-induced headache is significantly lower than in patients with ergotamine intake. This might be caused in part by the relatively short period of sumatriptan availability on the market. The new generation of serotonin-1B/D-receptor agonists in the treatment of headache should have a potential for overuse similar to that of traditional headache drugs.