Background: Internet interventions with and without therapist support have been found to be effective treatment options for harmful alcohol users. Internet-based therapy (IT) leads to larger and longer-lasting positive effects than Internet-based self-help (IS), but it is also more costly to provide. Objective: To evaluate the cost effectiveness and cost utility of Internet-based interventions for harmful use of alcohol through the assessment of the incremental cost effectiveness of IT compared with IS. Methods: This study was performed in a substance abuse treatment center in Amsterdam, the Netherlands. We collected data over the years 2008-2009. A total of 136 participants were included, 70 (51%) were female, and mean age was 41.5 (SD 9.83) years. Reported alcohol consumption and Alcohol Use Disorders Identification Test (AUDIT) scores indicated harmful drinking behavior at baseline. We collected self-reported outcome data prospectively at baseline and 6 months after randomization. Cost data were extracted from the treatment center's cost records, and sex- and age-specific mean productivity cost data for the Netherlands. Results: The median incremental cost-effectiveness ratio was estimated at €3683 per additional treatment responder and €14,710 per quality-adjusted life-year (QALY) gained. At a willingness to pay €20,000 for 1 additional QALY, IT had a 60% likelihood of being more cost effective than IS. Sensitivity analyses attested to the robustness of the findings. Conclusions: IT offers better value for money than IS and might therefore be considered as a treatment option, either as first-line treatment in a matched-care approach or as a second-line treatment in the context of a stepped-care approach. Trial Registration: Netherlands Trial Register NTR-TC1155; http://www.trialregister.nl/trialreg/ admin/rctview.asp?TC=1155 (Archived by WebCite at http://www.webcitation.org/ 6AqnV4eTU).