Objectives: Depressive disorders are significant causes of disease burden and are associated with substantial economic costs. It is therefore important to design a healthcare system that can effectively manage depression at sustainable costs. This article computes the benefit-to-cost ratio of the current Dutch healthcare system for depression, and investigates whether offering more online preventive interventions improves the cost-effectiveness overall. Methods: A health economic (Markov) model was used to synthesize clinical and economic evidence and to compute population-level costs and effects of interventions. The model compared a base case scenario without preventive telemedicine and alternative scenarios with preventive telemedicine. The central outcome was the benefit-to-cost ratio, also known as return-on-investment (ROI). Results: In terms of ROI, a healthcare system with preventive telemedicine for depressive disorders offers better value for money than a healthcare system without Internet-based prevention. Overall, the ROI increases from €1.45 ($1.72) in the base case scenario to €1.76 ($2.09) in the alternative scenario in which preventive telemedicine is offered. In a scenario in which the costs of offering preventive telemedicine are balanced by reducing the expenditures for curative interventions, ROI increases to €1.77 ($2.10), while keeping the healthcare budget constant. Conclusions: For a healthcare system for depressive disorders to remain economically sustainable, its cost-benefit ratio needs to be improved. Offering preventive telemedicine at a large scale is likely to introduce such an improvement. © 2014 American Association for Geriatric Psychiatry.