Low vitamin D and K status are both associated with an increased cardiovascular risk. New evidence from experimental studies on bone health suggest an interaction between vitamin D and K; however, a joint association with vascular health outcomes is largely unknown. To prospectively investigate whether the combination of low vitamin D and K status is associated with higher systolic and diastolic blood pressure in 402 participants and with incident hypertension in 231 participants free of hypertension at baseline. We used data from a subsample of the Longitudinal Aging Study Amsterdam, a population-based cohort of Dutch participants aged 55 to 65 years. Vitamin D and K status were assessed by 25-hydroxyvitamin D and dp-ucMGP (dephosphorylated uncarboxylated matrix gla protein) concentrations (high dp-ucMGP is indicative for low vitamin K status) in stored samples from 2002 to 2003. Vitamin D and K status were categorized into 25-hydroxyvitamin D <50/≥50 mmol/L and median dp-ucMGP <323/≥323 pmol/L. During a median follow-up of 6.4 years, 62% of the participants (n=143) developed hypertension. The combination of low vitamin D and K status was associated with increased systolic 4.8 mm Hg (95% confidence interval, 0.1–9.5) and diastolic 3.1 mm Hg (95% confidence interval, 0.5–5.7) blood pressure compared with high vitamin D and K status (P for interaction =0.013 for systolic blood pressure and 0.068 for diastolic blood pressure). A similar trend was seen for incident hypertension: hazard ratio=1.62 (95% confidence interval, 0.96–2.73) for the low vitamin D and K group. The combination of low vitamin D and K status was associated with increased blood pressure and a trend for greater hypertension risk.