Background: Tanacetum parthenium (feverfew) has been used traditionally to treat migraine, and although its mechanism of action is not fully understood, serotonin 5-HT receptor blocking effects have been suggested. T. parthenium and Salix alba (white willow) either alone or in combination (Mig-RL®) were recently shown to inhibit binding to 5-HT2A/2C receptors; T. parthenium failed to recognise 5-HT1D receptors, whereas S. alba or the combination did. It was hypothesised that S. alba in combination with T. parthenium may provide superior migraine prophylactic activity compared with T. parthenium alone. Methods: A prospective, open-label study was performed in 12 patients diagnosed with migraine without aura. Twelve weeks' treatment with T. parthenium 300mg plus S. alba 300mg (Mig-RL®) twice daily was administered to determine the effects of therapy on migraine attack frequency (primary efficacy criterion), intensity and duration (secondary efficacy criteria), and quality of life, together with tolerability for patients. Results: Attack frequency was reduced by 57.2% at 6 weeks (p < 0.029) and by 61.7% at 12 weeks (p < 0.025) in nine of ten patients, with 70% patients having a reduction of at least 50%. Attack intensity was reduced by 38.7% at 6 weeks (p < 0.005) and by 62.6% at 12 weeks (p < 0.004) in ten of ten patients, with 70% of patients having a reduction of at least 50%. Attack duration decreased by 67.2% at 6 weeks (p < 0.001) and by 76.2% at 12 weeks (p < 0.001) in ten of ten patients. Two patients were excluded for reasons unrelated to treatment. Self-assessed general health, physical performance, memory and anxiety also improved by the end of the study. Mig-RL® treatment was well tolerated and no adverse events occurred. Conclusion: The remarkable efficacy of Mig-RL® in not only reducing the frequency of migraine attacks but also their pain intensity and duration in this trial warrants further investigation of this therapy in a double-blind, randomised, placebo-controlled investigation involving a larger patient population.