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The safety of rapid carvedilol up-titration in patients with depressed left ventricular ejection fraction (LVEF) is unknown. The aim of the present work was to assess whether carvedilol can be used safely and rapidly up-titrated before hospital discharge in patients with left ventricular systolic dysfunction, with or without heart failure symptoms.We studied 611 patients with LVEF less than 0.4 in whom carvedilol was used during hospital admission.Mean age was 66 years, 23% were women and 372 had symptoms of heart failure. Carvedilol was initiated 3 days after admission (median); 594 patients (97%) were discharged alive, 27 (5%) without beta-blockers. Carvedilol up-titration during admission was performed in 65%. The mean time of up-titration was 1 week, with a mean increase of 16 mg/day. The discharge dose was higher in younger patients and in those weighing more than 70 kg. Only 30 patients (5%) were re-admitted during the first month after discharge. At the end of follow-up (mean 2.3 years), 497 patients were alive and transplant-free (81%). Carvedilol mean daily dose at the end of follow-up was 32.4 ± 22.2 mg and was related to the discharge dose. The absence of beta-blocker treatment at discharge was the most important independent predictor of long-term mortality (hazard ratio 3.1, 95% confidence interval 1.5–6.2, P = 0.002).Carvedilol up-titration is well tolerated in patients hospitalized with depressed LVEF, with or without heart failure, with a high compliance rate at discharge and in the long term.