BACKGROUND: Migraine is one of the most common neurological disorders that can severely overshadow people's quality of life, and Helicobacter pylori infection is a health problem in different societies. During the last two decades, many original studies have been conducted on the various aspects of the relationship between these two disorders; however, they have reported different and sometimes contradictory results. METHODS: This study was conducted based on the PRISMA protocol. We performed a comprehensive literature search in the online databases up to May 2023, and 22 studies that contained original data on the relationship between H. pylori infection and migraine headaches in adults were included. For performing the meta-analysis, we calculated the odds ratios (OR) and 95% confidence intervals (CI), using a random-effects model, and to determine the possible causes of heterogeneity, we conducted a subgroup meta-analysis. RESULTS: The overall OR for the association of H. pylori infection and migraine headaches through 493,794 evaluated individuals was 2.80 [95% CI = 1.75-4.48; I  = 89.20, p < 0.01], which reveals a statistically significant association between these disorders. It was found that the studies that were conducted in Asian regions and the recently published ones have clearly shown a higher association between migraine and H. pylori infection. On the other hand, migraine patients who are infected with H. pylori have similar signs and symptoms as H. pylori-negative migraineurs; meanwhile, the clinical trials conducted in this field strongly emphasize the benefits of eradicating H. pylori infection in migraine patients and have estimated its effectiveness in improving migraine headaches equivalent to current common migraine treatments. Furthermore, it was reported that white matter lesions were 2.5-fold higher on brain MRI in patients with H. pylori-positive migraine compared with H. pylori-negative migraineurs; however, the evidence does not support the role of oxidative stress in patients suffering from H. pylori infection and migraine and refuses the role of Cag-A-positive strains of H. pylori in migraine headaches. CONCLUSION: According to the currently available data, it seem reasonable that patients with a definite diagnosis of migraine who also suffer from gastrointestinal problems, undergo the H. pylori detection tests and if the evaluations are positive, H. pylori eradication treatment can be considered even before any migraine treatment.