<i>Objective:</i> To determine the effectiveness and safety of a new detoxification procedure in γ-hydroxybutyrate (GHB)-dependent patients. GHB is an endogenous inhibitory neurotransmitter and anesthetic agent that is being abused as a club drug. In many GHB-dependent patients a severe withdrawal syndrome develops that does not respond to treatment with high dosages of benzodiazepines and often requires an admission to an intensive care unit. <i>Methods:</i> Based on the knowledge of detoxification procedures in opioid and benzodiazepine dependence, we developed a titration and tapering procedure. A consecutive series of 23 GHB-dependent inpatients were transferred from illegal GHB (mostly self-produced) in various concentrations to pharmaceutical GHB. They were given initial doses that resulted in a balance between sedation and withdrawal symptoms. After this titration period, patients were placed on a 1-week taper. <i>Results:</i> We have found that after titration the patients experienced a low level of withdrawal symptoms. During tapering these symptoms decreased significantly and no patient developed a delirium or a psychosis. None of the patients had to be transferred to a medium or intensive care unit. <i>Conclusions:</i> This detoxification procedure proved to be safe and convenient in patients with moderate to severe GHB dependence.