An association between obesity and migraine has been observed in recent studies and it is supported by plausible biological mechanisms. The objective of this study is to evaluate the efficacy of frovatriptan and other triptans in the acute treatment of migraine, in patients enrolled in three randomized, double-blind, crossover, Italian studies and classified according to body mass index (BMI) levels, as normal weight or non-obese (NO, BMI 18.5-24.9 kg/m(2)) and overweight or obese subjects (O, BMI ≥ 25 kg/m(2)). 414 migraineurs with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). After treating up to three episodes of migraine in 3 months with the first treatment, patients switched to the alternate treatment for the next 3 months. The present analysis assessed triptan efficacy in 220 N and in 109 O subjects of the 346 individuals of the intention-to-treat population. The proportion of pain free at 2 h did not significantly differ between frovatriptan and the comparators in either NO (30 vs. 34 %) or O (24 vs. 27 %). However, the rate of pain free at 2 h was significantly (p < 0.05) larger in NO than in O, irrespective of the type of triptan. Pain relief at 2 h was also similar between drug treatments for either subgroup. Pain relapse occurred at 48 h in significantly (p < 0.05) fewer episodes treated with frovatriptan in both NO (26 vs. 36 %) and O (27 vs. 49 %). The rate of 48-h relapse was similar in NO and O with frovatriptan, while it was significantly (p < 0.05) higher in O with the comparators. Frovatriptan, in contrast to other triptans, retains a sustained antimigraine effect in NO and even more so in O subjects.