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BACKGROUND AND AIMS Clinical trials have shown that intensive low-density lipoprotein cholesterol (LDL-C) lowering improves cardiovascular outcomes among patients with atherosclerotic cardiovascular disease (ASCVD), but data are limited in real clinical practice, particularly for patients with ASCVD inform different territories. METHODS FRENA was a prospective registry of consecutive outpatients with coronary, cerebrovascular or peripheral artery disease. We compared the incidence of recurrent events in patients with sustained LDL-C levels <70 mg/dl compared with those with ≥70 mg/dl. RESULTS As of December 2018, 1,182 patients were eligible for this study. Of these, 172 (14.5%) had mean LDL-C levels ≤70 mg/dL, and 1010 (85.5%) had <70 mg/dL. Their clinical characteristics at baseline were similar. During 5 years of follow-up, 252 patients (21%) suffered major adverse cardiovascular events (MACE). The incidence rates of MACE were 3.42 events per 100 patient-years (95% confidence interval (95% CI) 2.17-5.14) in patients with levels <70 mg/dL and 5.57 (95% CI. 4.87-6.34) in those with ≥70 mg/dL; the rate ratio was 0.61 (95% CI. 0.39-0.92), p=0.019. On multivariable analysis, patients with LDL-C levels <70 mg/dL were at lower risk for MACE (hazard ratio [HR]: 0.61 (95% CI. 0.39-0.93) p<0.05). MACE reduction was driven by a decrease in coronary and peripheral events with no significant effect on stroke. CONCLUSIONS Long term sustained LDL-C <70 mg/dl in the clinical practice is associated with reduction in cardiovascular and peripheral vascular events with no apparent effect on stroke.