Caffeine, a popular ergogenic supplement, induces neural and vascular changes that may influence coagulation and/or fibrinolysis at rest and during exercise. Purpose The purpose of this study was to assess the effect of a single dose of caffeine on measures of coagulation and fibrinolysis before and after a single bout of high-intensity exercise. Methods Forty-eight men (age, 23 3 yr; body mass index, 24 3 kgm(-2)) completed two trials, with 6 mgkg(-1) of caffeine (CAFF) or placebo (PLAC), in random order, followed by a maximal cycle ergometer test. Plasma concentrations of fibrinogen, factor VIII antigen, active tissue plasminogen activator (tPA:c), tissue plasminogen activator antigen (tPA:g), and active plasminogen activator inhibitor-1 (PAI-1:c) were assessed at baseline and immediately after exercise. Results Exercise led to significant changes in tPA:c ( 8.5 +/- 4.36 IUmL(-1) for CAFF, 6.6 +/- 3.7 for PLAC), tPA:g ( 2.4 +/- 3.2 ngmL(-1) for CAFF, 1.9 +/- 3.1 for PLAC), fibrinogen ( 30.6 +/- 61.4 mgdL(-1) for CAFF, 28.1 +/- 66.4 for PLAC), and PAI-1:c ( -3.4 +/- 7.9 IUmL(-1) for CAFF, -4.0 +/- 12.0 for PLAC) (all P < 0.05), but no effect of condition or time-condition interactions were observed. Main effects of time, condition, and a significant time-condition interaction were observed for factor VIII, which increased from 1.0 +/- 0.4 IUmL(-1) to 3.3 +/- 1.3 IUmL(-1) with CAFF and 1.0 +/- 0.4 IUmL(-1) to 2.4 +/- 0.9 IUmL(-1) with PLAC. Conclusions Coagulation potential during exercise is augmented after caffeine intake, without a similar increase in fibrinolysis. These results suggest caffeine intake may increase risk of a thrombotic event during exercise.