<jats:sec id="S0007125018000107_sec_a1"><jats:title>Background</jats:title><jats:p>Web-based interventions are effective in reducing depression. However, the evidence for the cost-effectiveness of these interventions is scarce.</jats:p></jats:sec><jats:sec id="S0007125018000107_sec_a2"><jats:title>Aims</jats:title><jats:p>The aim is to assess the cost-effectiveness of a web-based intervention (GET.ON M.E.D.) for individuals with diabetes and comorbid depression compared with an active control group receiving web-based psychoeducation.</jats:p></jats:sec><jats:sec id="S0007125018000107_sec_a3" sec-type="methods"><jats:title>Method</jats:title><jats:p>We conducted a cost-effectiveness analysis with treatment response as the outcome and a cost-utility analysis with quality-adjusted life-years (QALYs) alongside a randomised controlled trial with 260 participants.</jats:p></jats:sec><jats:sec id="S0007125018000107_sec_a4" sec-type="results"><jats:title>Results</jats:title><jats:p>At a willingness-to-pay ceiling of €5000 for a treatment response, the intervention has a 97% probability of being regarded as cost-effective compared with the active control group. If society is willing to pay €14 000 for an additional QALY, the intervention has a 51% probability of being cost-effective.</jats:p></jats:sec><jats:sec id="S0007125018000107_sec_a5" sec-type="conclusion"><jats:title>Conclusions</jats:title><jats:p>This web-based intervention for individuals with diabetes and comorbid depression demonstrated a high probability of being cost-effective compared with an active control group.</jats:p></jats:sec><jats:sec id="S0007125018000107_sec_a6"><jats:title>Declaration of interest</jats:title><jats:p>S.N., D.D.E., D.L., M.B. and B.F. are stakeholders of the Institute for Online Health Trainings, which aims to transfer scientific knowledge related to this research into routine healthcare.</jats:p></jats:sec>