Aim: To compare and observe the curative effect of tylox and tramadol in treating moderate-to-severe migraine and tension headache. Methods: Fifty-two adult patients with moderate-to-severe migraine and tension headache were divided into tylox group (n = 25) and tramadol group (n = 27) by random number table method. Patients took one capsule of tylox or one tablet of tramadol orally for treatment. The numeric rating scales (NRS), numeric changes, efficacy rate of relieving pain and the dysreaction were observed before and after treatment. Results: The difference of NRS in patients of hemicrania who took tylox (group 1) did not have obvious significance. The NRS value of the patients of hemicrania who took tramadol (group 2) and the patients of tension headache taking tylox (group 3) or taking tramadol (group 4) were 7.48 ± 1.75, 6.03 ± 2.47 and 6.96 ± 2.39, which decreased to 3.58 ± 3.26, 1.25 ± 1.53 and 2.32 ± 2.30 after treatment. Each of the values was significantly decreased (P < 0.01), and the NRS values in group 2 and group 3 were obvious lower than that in group 1 (comparison between group 1 and group 2: t = 2.369, P = 0.029; comparison between group 1 and group 3: t = 6.012, P = 0.000). The efficacy rate in group 3 was significantly higher than that in group 1 (13%, P = 0.020). The difference of the incidence of side effects among groups was not significant. Conclusion: The effect of tylox used for tension headache is better, and tramadol is suitable for migraine and tension headache. Both of them can be used when other drugs cannot control these moderate-to-severe pains.