We tested whether increased concentrations of the acute-phase reactant fibrinogen correlate with pulmonary function and rate of chronic obstructive pulmonary disease (COPD) hospitalization. We measured plasma fibrinogen and forced expiratory volume in 1 s (FEV(1)), and assessed prospectively COPD hospitalizations in 8,955 adults from the Danish general population. Smokers with plasma fibrinogen in the upper and middle tertile (> 3.3 and 2.7-3.3 g/L) had 7% (95% confidence interval [CI]: 5-8%) and 2% (0-3%) lower percentage predicted FEV(1) than smokers with fibrinogen in the lower tertile (< 2.7 g/L). The equivalent decreases in nonsmokers were 6% (4-7%) and 0% (-1-2%), respectively. Individuals with plasma fibrinogen in the upper and middle tertile had COPD hospitalization rates of 93 and 60 compared with 52 per 10,000 person-years in individuals with fibrinogen in the lower tertile (log-rank: p < 0.001 and p = 0.31). After adjusting for age, body mass index, sex, pack-years, and recent respiratory infections, relative risks for COPD hospitalization were 1.7 (95% CI: 1.1-2.6) and 1.4 (0.9-2.1) in individuals with fibrinogen in the upper and middle versus lower tertile. In conclusion, elevated plasma fibrinogen was associated with reduced FEV(1) and increased risk of COPD. This could not be explained by smoking alone.