Background: An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations. Objective: We studied the effect of coffee consumption on plasma homocysteine in a crossover trial. We used unfiltered coffee so as to include the possible effects of coffee diterpenes, which are removed by filtering. Design: Sixty-four healthy volunteers (31 men and 33 women) with a mean (±SD) age of 43 ± 11 y were randomly assigned to 2 groups. One group (n = 30) drank 1 L unfiltered cafetière (French press) coffee daily for 2 wk. Such coffee is rich in the cholesterol-raising diterpenes kahweol and cafestol. The other group (n = 34) received water, milk, broth, tea, and chocolate drinks instead of coffee. After a washout period of 8 wk, both groups received the alternate intervention for another 2 wk. Results: Consumption of 1 L unfiltered coffee/d for 2 wk significantly raised fasting plasma homocysteine concentrations by 10°from 12.8 to 14.0 mmol/L. Conclusions: Unfiltered coffee increases plasma homocysteine concentrations in volunteers with normal initial concentrations. It is unclear whether the effect is caused by the cholesterol-raising diterpenes present exclusively in unfiltered coffee or by factors that are also present in filtered coffee.