ObjectivesTo examine the longitudinal relationship between cardiovascular fitness in young adult men and future risk of migraine and to estimate eventual differential effects among categories of body mass index (BMI) and blood pressure.DesignNational, prospective, population-based cohort study.SettingSweden 1968–2014.Participants18-year-old Swedish men (n=1 819 828) who underwent mandatory military conscription examinations during the years 1968–2005.Primary and secondary outcomesThe primary outcome was the first dispensation of prescribed migraine-specific medication, identified using the Swedish Prescribed Drug Register. The secondary outcome was documented migraine diagnosis from the Swedish National Hospital Register.ResultsDuring follow-up, 22 533 men filled a prescription for migraine-specific medication. After confounding adjustment, compared with high cardiovascular fitness, low and medium fitness increased the risk of migraine-specific medication (risk ratio (RR)_low: 1.29, 95% CI 1.24 to 1.35; population attributable fraction: 3.6%, 95% CI 1.7% to 5.3% and RR_medium: 1.15, 95% CI 1.12 to 1.19; population attributable fraction: 8.0%, 95% CI 4.0% to 11.7%). To assess potential effect measure modification, stratified analyses of these association by levels of BMI and blood pressure showed that lower fitness levels increased risk of migraine across all groups except among underweight men or men with high diastolic blood pressure.ConclusionsYoung men with a lower cardiovascular fitness had a higher long-term risk of developing pharmacological prescription-requiring migraine. This study contributes with information regarding risk factors for migraine in men, an understudied population in migraine research.