In cross-sectional studies, elevated homocysteine levels are associated with higher blood pressure, but it remains unclear whether plasma homocysteine is a risk factor for hypertension. In a prospective nested case-control study, participants who developed hypertension (n=396) had significantly higher levels of baseline plasma homocysteine (12.6 mol/l) than matched controls (11.8 mol/l, P=0.03); compared to those in the lowest quintile, those in the highest quintile had a crude relative risk (RR) of 1.56 (95% confidence interval (CI), 0.98-2.48; P for trend=0.10) and a multivariable RR of 1.63 (95% CI, 0.97-2.74; P for trend=0.13). Higher plasma homocysteine levels at baseline were associated with an increased but non-significant risk of incident hypertension that was minimally affected by multivariable adjustment.