Background: To investigate the acute effect of caffeine on intraocular pressure and retrobulbar blood flow velocity. Methods: In this randomized, double-masked, placebo-controlled, prospective study, we examined the effects of single 300-mg oral administration of caffeine on retrobulbar arteries' hemodynamics by using color Doppler ultrasonography imaging in healthy human volunteers. The subjects were divided into two groups; group 1 received a 300-mg caffeine tablet and group 2 received placebo. Measurements were obtained in two eyes at baseline, and 1 hr after acute ingestion of caffeine. Blood pressure, pulse rate, and intraocular pressure were monitored. Results: When compared with placebo, no significant change in mean blood pressure or intraocular pressure was observed after administration of caffeine. No significant differences were detected in the peak systolic and end diastolic velocities of retrobulbar arteries, compared with baseline values. Resistive index of ophthalmic, central retinal, and short posterior nasal ciliary artery were significantly increased after oral application of caffeine in group 1 (p 0.05). Conclusion: The vascular resistance of the retrobulbar vessels appears to be altered by caffeine consumption. Further studies are needed to investigate the effects of caffeine on hemodynamics in patients with glaucoma.