Purpose: Screening for asymptomatic left ventricular (LV) dysfunction can either affect clinical management and outcome if positive or avoid cost-uneffective strategies if negative. For this purpose NT-proBNP has proved to be an effective tool. The PROBE-HF is a population-based study aimed to assess the prevalence of asymptomatic left ventricular dysfunction in subjects at risk of heart failure and to evaluate the role of NT-proBNP in the diagnostic pathway. Methods: Out of 1162 subjects affected by systemic hypertension and/or type 2 diabetes randomly selected from the database a large association of 110 general practitioners involved in 130,000 citizens primary care, 1012 (87%) showed a good quality echo (486 males, 48%, 526 females, 52%, age 66±8 yrs). LV dysfunction was diagnosed according to current ESC Guidelines. NT-proBNP plasma levels were determined using immunoassay. esults: Among 379/1012 subjects with LV dysfunction (37.5%) 368 (36.4%, group A) showed an isolated diastolic dysfunction, 11 (1.1%, group B) a systolic one. 633 subjects (62.5%, group C) resulted free from LV dysfunction. NT-proBNP mean and median values resulted significantly different as follows: group A 170±206 and 115 ng/L; group B 859±661 and 551 ng/L; group C 92±169 and 65 ng/L (p for mean and median values =.000). A NT-proBNP >200 ng/L was independently predicted by age (65-74 years: OR = 2.6, IC95% 1.5-4.4, p = .000; ≥75 years: OR = 6.6, IC95% 3.7-11.6, p = .000), mitral regurgitation (OR = 1.8, IC95% 1.07-2.9, p = .02), diastolic dysfunction (mild: OR = 2.3, IC95% 1.5-3.4, p =.000; moderate-to-severe: OR = 15.5, IC95% 7.4-32.8, p =.000), and systolic dysfunction (OR = 96.4, IC95% 11.5-807.6, p = .000). Best cut-off values: 125 ng/L for females <75 yrs (sens 100%, spec 73.6%, NPV 100%, AUC .75); 400 ng/L for females ≥75 yrs (sens 100%, spec 88.8%, NPV 100%, AUC .89); 125 ng/L both for males < and ≥75 yrs (respectively, sens 93.7% and 100%, spec 83.9% and 53%, NPV 99.7% and 100%, AUC .88 and .56) Conclusions: NT-proBNP shows an excellent negative predictive value in the diagnosis of asymptomatic LV dysfunction in diabetic or hypertensive patients. Moreover, its specificity appears to be higher than previously reported. Different NT-proBNP cut-off values according to age and gender could help general practitioners in the management of subjects at risk of heart failure.