Cross-sectional and limited prospective evidence has suggested that inflammatory markers may predict for the risk of atrial fibrillation (AF). In a prospective cohort study, we studied the risk of incident AF among 8,870 women and men free of cardiovascular disease enrolled in the Copenhagen City Heart Study. We measured plasma fibrinogen and serum albumin levels at a study visit from 1991 to 1994. We identified 286 subsequent cases of AF during a mean of 7.5 years of follow-up by a validated nationwide registry of all hospitalizations. The fibrinogen levels at baseline were associated with a higher risk of AF, with a multivariate-adjusted hazard ratio for the highest versus lowest quartiles of 1.98 (95% confidence interval [CI] 0.94 to 4.17) among men and 2.14 (95% CI 1.15 to 3.96) among women. The albumin levels were inversely associated with the risk of AF among women (hazard ratio 0.47, 95% CI 0.28 to 0.77) but not among men (hazard ratio 1.01, 95% CI 0.56 to 1.84). Additional adjustment for cases of coronary heart disease, congestive heart failure, and stroke that occurred during follow-up did not attenuate these associations. In conclusion, higher levels of fibrinogen and lower levels of albumin were prospectively associated with a higher risk of AF, even accounting for their relation with the risk of cardiovascular disease. These findings support the hypothesis that inflammation contributes to the etiology of AF.