Objectives: This study aims to investigate the efficacy of acupuncture in preventing migraine attacks. Patients and methods: Between December 2013 and June 2014, a total of 54 patients with a diagnosis of migraine in our neurology clinic were randomized into two groups. Venlafaxine was administered for three months to one group (drug therapy group: 4 males, 21 females; mean age 32.0 +/- 9.1 years; range, 18 to 65 years), while the other group was treated with acupuncture (acupuncture group: 5 males, 24 females; mean age 30.3 +/- 7.4 years; range, 18 to 65 years). The control group consisted of a total of 29 healthy individuals (7 males, 22 females; mean age 30.3 +/- 7.4 years; range 18 to 65 years). Blood serotonin levels were assessed before and after treatment along with visual analog scale (VAS) and Migraine Disability Assessment (MIDAS) in both groups. Results: There was no statistically significant difference in the mean analgesic use before and after the treatment and VAS and MIDAS scores between the acupuncture and drug therapy groups (p>0.05). The number and duration of attacks was found to be significantly lower in both groups, compared to the pre-treatment values (p<0.0001). The serotonin levels in the acupuncture and drug therapy groups were significantly higher compared to the pre-treatment values (p<0.001). Serotonin levels were found to be significantly lower in healthy individuals compared to the study groups (p<0.0001). Conclusion: Based on our study findings, acupuncture may be an effective option in the migraine prophylaxis.