Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol dependent (AD) patients in a series of small randomized controlled trials (RCTs) with a fixed dose. These results needed to be confirmed and the SMO dose-response relationship to be investigated to establish the optimal dose. Moreover, heterogeneity of SMO efficacy was identified, and rare cases of SMO abuse or misuse were reported. In this thesis, we report on a large Phase III RCT that confirmed the efficacy of SMO in the MoA in AD patients. We also report on a large Phase IIb RCT testing different doses of SMO with results suggesting that the SMO dose (in mg/kg) should be adjusted according to baseline alcohol consumption: the more alcohol consumed at baseline, the higher the SMO dose needs to be. Substantial heterogeneity of SMO efficacy was identified within these two RCTs with SMO efficacy being negatively correlated with placebo response. The effect of two potential effect modifiers, i.e., population severity and treatment duration, on SMO efficacy and on placebo response, was tested using subgroup analysis and (network) meta-regression analysis. It was shown that high-severity population and longer treatment duration were associated with larger SMO effects and a smaller placebo response within and across trials. SMO was (most) effective in the high-severity population which includes (very) heavy drinkers, a population with a life expectancy of 47–61 years. SMO was well-tolerated. Importantly, the Phase IIb tested the safety of a new SMO abuse/misuse deterrent formulation. No cases of abuse, overdose, or misuse were reported with this new formulation. These findings support the efficacy, safety, and the positive benefit-risk of SMO in the treatment of AD patients.