Introduction: There is growing evidence that computer-delivered or computer-assisted forms of cognitive behavior therapy (CCBT) are helpful, but cost-effectiveness versus standard therapies is not well established. Objective: To evaluate the cost-effectiveness of a therapist-supported method for CCBT in comparison to standard cognitive behavior therapy (CBT). Methods: A total of 154 drug-free major depressive disorder outpatients were randomly assigned to either 16 weeks of standard CBT (up to twenty 50-min sessions) or CCBT using the Good Days Ahead program (including up to 5.5 h of therapist contact). Outcomes were assessed at baseline, weeks 8 and 16, and at 3 and 6 months post-treatment. Economic analyses took into account the costs of services received and work/social role impairment. Results: In the context of almost identical efficacy, a form of CCBT that used only about one third the amount of therapist contact as conventional CBT was highly cost-effective compared to conventional therapy and reduced the adjusted cost of treatment by USD 945 per patient. Conclusions: A method of CCBT that blended internet-delivered modules and abbreviated therapeutic contact reduced the cost of treatment substantially without adversely affecting outcomes. Results suggest that use of this approach can more than double the access to CBT. Because clinician support in CCBT can be provided by telephone, videoconference, and/or email, this highly efficient form of treatment could be a major advance in remote treatment delivery.