Objective To assess the effect of allopurinol use on the risk of incident atrial fibrillation (AF) in the elderly. Methods We used the 5% random Medicare Claims data from 2006 to 2012 to examine the association of allopurinol use and incident AF in a cohort of patients with an absence of AF at baseline (at least 365 days). Multivariable-Adjusted Cox regression analyses compared allopurinol exposed and non-exposed periods for the risk of AF, controlling for age, sex, race, Charlson-Romano comorbidity index and use of statins, diuretics, ACE inhibitors and β-blockers. HR with 95% CIs was calculated. Sensitivity analyses considered a longer baseline period (365 days vs 183 days) and individual comorbidities. Results There were 9244 episodes of incident allopurinol use in 8569 beneficiaries, of which 1366 episodes (14.8%) had incident AF. In multivariableadjusted analyses, allopurinol use was associated with an HR of 0.83 (95% CI 0.74 to 0.93) for incident AF. In a separate multivariable-Adjusted model, compared with no allopurinol use, longer allopurinol use durations were associated with a lower HR of AF: 180 days-2 years, 0.85 (95% CI 0.73 to 0.99) and ≥2 years, 0.65 (95% CI 0.52 to 0.82). Other factors significantly associated with a higher hazard of AF were: Age 75-<85 years and ≥85 years, higher Charlson index score and current β-blocker use. Sensitivity analyses confirmed these findings with minimal/no attenuation of HRs. Conclusions Allopurinol use was associated with a reduced risk of incident AF in the elderly, especially its use for >6 months duration. Future studies should assess the mechanisms underlying this beneficial effect of lopurinol.