OBJECTIVES: To evaluate the impact on alcohol-dependent patients’ reported outcomes (PROs) from the as-needed use of nalmefene versus placebo in reduction of alcohol consumption. METHODS: Two 6-month randomized, double-blind, placebo-controlled, efficacy studies assessing nalmefene 18mg (base) were conducted in Europe (ESENSE 1 [NCT00811720]; ESENSE 2 [NCT00812461]). All patients took part in a motivational intervention (BRENDA) to support behavioural change and adherence to treatment. The Short Form Health Survey (SF-36), the EuroQol-5 Dimensions (EQ-5D) and the Drinker Inventory of Consequences (DrInC-2R) questionnaires were administered at baseline, weeks 12 and 24. Post-hoc analyses of the pooled subgroup of patients with a high drinking risk level (men:>60 g/day; women:>40 g/day) assessed change from baseline using mixed models repeated measures. RESULTS: At baseline, the sample comprised 641 patients: 322 in the placebo group, 319 in the nalmefene group. The SF-36 Mental Component Score (MCS) and the EQ-5D health state score were 40.9±12.6 and 67.9±17.2 in the placebo group; 40.9±11.9 and 68.9±17.7 in the nalmefene group. The MCS improvement at week 24 was significantly correlated to HDD (Heavy Drinking Day) and TAC (Total Alcohol Consumption) reduction and was significantly larger for the nalmefene group compared to placebo (p=0.0008): the means change from baseline were 5.74±0.79 and 2.65±0.78 in the nalmefene and placebo groups respectively. For the EQ-5D, the mean change from baseline for nalmefene compared to placebo for the health state score and the utility index score was 3.46 (p=0.0124) and 0.03 points (p=0.0445) respectively. The mean DrInC-2R total score change from baseline to week 24 was significantly correlated to HDD and TAC reduction.  The improvement, indicating less alcohol-related problems, was significantly larger with nalmefene (17.86±1.31) than for placebo (14.64±1.30) (p=0.0292). CONCLUSIONS: As-needed use of nalmefene for reduction of alcohol consumption leads to statistically significantly larger improvements of alcohol dependent patients' PROs versus placebo.