The objective of this study was to compare acamprosate with placebo in the treatment of alcohol-dependent patients during a 6-month post-detoxification treatment and a 3-month medication-free follow-up. Patients (n = 330) were detoxified and randomized to treatment with acamprosate (1998 mg/day) or placebo within an out-patient programme including medical counselling, psychotherapy and self-help groups. The main outcome criterion was drinking behaviour as assessed by: abstinence/relapse ratio, cumulative abstinence duration (CAD) and the period of continued abstinence. Anxiety, depression and craving were also monitored. Intention to treat (ITT) statistical principles were followed. Twenty-five per cent of patients dropped out over the first 6 months. At the end of the treatment period, the abstinence rate was 57.9% for acamprosate and 45.2% for placebo (P = 0.03). The CAD was 110+/-77 days for acamprosate and 89+/-77 days for placebo (P = 0.016). Patients on acamprosate had a higher continuous abstinence rate and experienced less severe relapses. No differential effect was noted for anxiety, depression or craving. Treatment remained positive, but not significant, 3 months after termination of study medication. No significant difference in adverse events was noted between treatment groups. Acamprosate treatment over 180 days was consistently more effective than placebo to maintain abstinence and to diminish relapse severity.