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Using a large clinical multi-site prospective chronic heart failure registry, we sought to determine (i) implementation of guidelines over time and (ii) adjusted survival benefit there from.Clinical characteristics, mortality, and medication according to guidelines [guideline adherence index (GAI) for ACE-inhibitors or angiotensin receptor blockers, beta-blockers, aldosterone antagonists] were compared for 1481 patients included from 1994 to 2000 and 1811 patients from 2001 to 2007. The co-morbidity corrected GAI significantly increased from 1994–2000 to 2001–07 (P < 0.001). Concomitantly, 1- and 3-year mortality decreased (14.1–4.8 and 29.5–10.9%, respectively, P < 0.001 each). No interaction with age or sex was noted (P = 0.06, P = 0.25, respectively), though age determined complete medication according to guidelines (P < 0.05). The GAI was a significant predictor of lower overall mortality (adjusted HR per 10% increase: 0.92; 95% CI: 0.88–0.97; P = 0.001), again independent from age or sex. Results were essentially unchanged after controlling for co-morbidities and other potential confounders.This study shows that increased use of medication according to guidelines might occur without interventions targeting medication use. It seems to be associated with a substantial improvement in survival. Even though causality cannot be proven, the findings underscore the importance of meticulous implementation of guidelines irrespective of age, sex, or co-morbidities.