In this study, we compared the efficacy and tolerability of the combination of paracetamol 1,000 mg + caffeine 130 mg (PCF) with sumatriptan 50 mg (SUM) in migraine attacks. This was a multi-center randomized double-blind, double-dummy, cross-over controlled trial. The efficacy was assessed by the sum of pain intensity differences, the curve of mean pain intensity, the number of pain free at 2 h, and the total pain relief. Tolerability was assessed by recording adverse events within 4 h after drug assumption and evaluating the global judgement of patients. The comparison of these parameters did not show differences between the two drugs which resulted absolutely overlapping in pain relief and patients evaluation. In conclusion, we confirm the efficacy and safety of PCF such as SUM in the treatment of migraine attacks.