Objectives: To assess the effects of a tailored, multifaceted intervention in primary care on the level of patients' alcohol consumption and to investigate which patient and organizational factors determine a reduction in alcohol consumption. Methods: This was a cluster randomized, controlled trial conducted among primary care practices in The Netherlands. Data from 6318 patients were available, of whom 712 patients from 70 practices were hazardous or harmful alcohol users. The improvement (intervention) program combined professional, organizational, and patient-directed activities. The emphasis was on educational training for general practitioners and support visits by a trained facilitator, tailored to the participants' needs and attitudes. The primary outcome was the proportion of patients with hazardous or harmful alcohol consumption, as measured with the Alcohol Use Disorders Identification Test, who reduced their levels of alcohol consumption to low-risk levels after 2 years. Results: Of the hazardous and harmful alcohol users, a substantial proportion (41.6%) reduced their alcohol consumption to a low-risk level. The trial revealed a significant difference in favor of the control group: 35.5% of the patients with hazardous and harmful alcohol consumption in general practitioners' practices in the intervention group and 47.0% of this patient group in general practitioners' practices in the control group reduced their alcohol consumption to a low-risk level (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.43-0.90). Older age (OR, 1.02; 95% CI, 1.01-1.03), female sex (OR, 2.00; 95% CI, 1.26-3.19), and attitudes toward alcohol use seemed to be the most important predictors for the reduction of alcohol use to a low-risk level. Patients who considered it important to reduce alcohol consumption and patients who believed that less alcohol complicates relaxation were less likely to reduce their alcohol use to a low-risk level (OR, 0.39; 95% CI, 0.19-0.80 and OR, 0.58; 95% CI, 0.37-0.90, respectively). Characteristics of the general practices, however, were not associated with reduced alcohol use. Conclusions: Our results suggest that the intervention has been counterproductive because the proportion of patients reducing their levels of alcohol consumption to low-risk levels was lower in the intervention group compared with the control group. Furthermore, our study demonstrated that patients' attitudes toward alcohol use are an important determinant of the success of the program. Therefore, future research should focus on the effectiveness of methods to change patients' attitudes.