Introduction: Epidemiologic studies have identified low 25(OH) vitamin D (vitD) levels as an independent risk factor for cardiovascular (CV) disease and total mortality. However, the actual vitD level threshold below which cardiovascular risk increases is not clearly established. Hypothesis: Among a large general population of patients undergoing clinical testing for vitD, a specific threshold level below which CV risk rises can be identified. Methods: All patients in the Intermountain Healthcare clinical database with at least one vitD level and no history of heart or renal failure were identified. Baseline vitD levels were stratified into four groups (<15 ng/mL [9.2%], 15-29 ng/mL [45.3%), 30-44 ng/mL [32.6%], ≥45 ng/mL [12.8%]) and followed for up to 3 (n=140,056) or 5 (n=69,887) years for MACE including death, new diagnosis of coronary artery disease (CAD), myocardial infarction (MI), stroke and incident heart (HF) or renal (RF) failure. Five year MACE hazard ratios (HRs) comparing groups were calculated by Cox regression, adjusting for 17 baseline variables. Results: A total of 234,920 patients (age 48±20 y, female: 72%, diabetes: 12%, hypertension: 29%, hyperlipidemia: 30%) were studied. Event rates at 3 and 5-y by vitD group are shown in the Table. Adjusted 5 yr MACE HRs, using vitD<15 ng/mL as the comparator, were HR=0.80(p<0.0001), HR=0.75(P<0.0001) and HR=0.75(p<0.0001) for vitD ≥45 ng/mL, 30-44 ng/mL and 15-29 ng/mL respectively, and using vitD≥45 ng/mL as the comparator, were HR=1.34(p<0.0001), 1.07(p=0.02) and 1.00(p=0.93) for vitD<15 ng/mL, 15-29 ng/mL and 30-44 ng/mL respectively. Conclusions: Among a large general population undergoing clinical testing for vitD, a 35% increased CV risk was identified, and was limited to only those with vitD levels <15 ng/mL, comprising 9.2% of the entire group. It is therefore likely that any clinical cardiovascular benefits from vitD supplementation will be limited to those with the lowest baseline vitD levels.