Depression is one of the most prevalent mental health disorders and is estimated to become the leading cause of disability worldwide by 2030. Increasing access to effective treatment for depression is a major societal challenge. In this context, the increasing use of computers in the form of laptops or smartphones has made it feasible to increase access to mental healthcare through digital technology. In this study, we examined the effectiveness of a 14-week therapist-guided Internet-delivered program for patients with major depression undergoing routine care. From 2015 to 2018, 105 patients were included in the study. For depressive symptoms, we identified significant within-group effect sizes (post-treatment: d = 0.96; 6-month follow-up: d = 1.21). We also found significant effects on secondary anxiety and insomnia symptoms (d = 0.55-0.92). Clinically reliable improvement was reported by 48% of those undergoing the main parts of the treatment, whereas 5% of the participants reported a clinically significant deterioration. However, a large proportion of patients showed no clinically reliable change. In summary, the study identified large treatment effects, but also highlighted room for improvement in the usability of the treatment.