Aims: To investigate the association between circulating Chlamydia pneumoniae (C pneumoniae) immunoglobulin G (IgG) antibody and migraine in Indian patients. Methods: A total of 300 migraine patients and 150 age-matched and sex-matched controls were recruited from the Department of Neurology at Yashoda Hospital in Hyderabad, India, during the study period between August 2011 and July 2013. All patients and controls were assessed for the presence of the C pneumoniae IgG antibody and also C-reactive protein (CRP) as well as for depression, which was assessed by the Hamilton Depression Rating Scale (HDRS). Results: Of the patients with migraine, 69% were female and the mean age ± standard deviation (SD) was 45.8 ± 4.8 years (range 18 to 62 years). The C pneumoniae IgG antibody was present in 151 of the patients (50.3%; P .0001), CRP in 180 (60%; P .0001), depression in 270 (90%; P .0001), and history of sleep disturbances in 70 (23.3%; P .0001); all measurements were significantly higher in migraine patients compared with controls. After adjustment for multiple logistic regression analyses, C pneumoniae IgG antibody positivity (odds ratio [OR] 2.6; 95% confidence interval [CI] = 1.3 to 3.7), CRP positivity (OR 6.2; 95% CI = 3.3 to 11.6), mild depression (OR 16.9; 95% CI = 6.5 to 39.4), and history of sleep disturbance (OR 2.1; 95% CI = 1.1 to 3.1) were independently associated with migraine. Conclusion: This study showed that the presence of C pneumoniae IgG antibody was independently associated with migraine in Indian patients. Keywords: C pneumoniae positive, C-reactive protein, history of sleep disturbance, Indian population, migraine