Moderate to severe migraine attacks are treated with triptans. However, about 25% of migraineurs fail to respond to triptans. We investigated the involvement of gene polymorphisms, personality traits and characteristics of headache, and made a scoring system for prediction of clinical response to triptans in patients with migraine. Gene polymorphisms including serotonin (5-HT)(1B) receptor G861C and dopamine receptor 2 (DRD2) C939T, personality traits and characteristics of headache were investigated in 46 consistent responders and 14 inconsistent responders to triptans. The multivariate stepwise logistic regression analysis revealed that age, periorbital/deep orbital pain and C/C genotype carrier at DRD2 C939T were significant factors that contributed independently to the negative response to triptans in patients with migraine. Their odds ratios were 6.329 (40-69 vs. 20-39 years, 95% CI 1.441-27.778), 6.772 (no vs. yes, periorbital/deep orbital pain, 95% CI 1.159-39.580) and 14.085 (non-C/C vs. C/C genotype at DRD2 C939T, 95% CI 1.253-166.667), respectively. The predictive index (PI) of clinical response to triptans in patients with migraine was calculated using these three factors. The score in inconsistent responders (1.6 ± 0.6) was significantly higher than that in consistent responders (0.8 ± 0.7, P < 0.001). Sensibility of low-score (RI = 0) group was 100%, and specificity of high-score (PI ≥ 2) group was 87%. The proposed scoring system should in the future be the object of larger studies to confirm its validity.