Digitally delivered interventions for depression vary in many aspects, including their therapeutic orientation, depth of content, interactivity, individual tailoring, inclusion of multimedia, cost, and effectiveness. However, their effectiveness is rarely examined in intervention-specific meta-analyses. An earlier meta-analysis of eight randomized controlled trials (RCT) demonstrated the effectiveness of a tailored, integrative digital intervention (deprexis), which is delivered via the Internet. This updated meta-analysis of twelve deprexis-specific RCT with a total of N = 2901 participants confirmed the effectiveness of deprexis for depression reduction at post-intervention (g = 0.51, 95% CI: 0.40-0.62, I2 = 26%). Results were analogous when study quality, screening and randomization procedure were taken into account. Clinician guidance, developer-involvement, setting (community vs. clinical), and initial symptom severity did not have statistically significant effects on the effect size, and there was no evidence of publication bias. Thus, these findings demonstrate that deprexis can facilitate clinically relevant reduction of depressive symptoms over 8-12 weeks across a broad range of initial symptom severity, and that the intervention can be combined with other forms of depression treatment. There is now a need to study the intervention's implementation in routine care settings as well as its long-term effectiveness and cost-effectiveness in diverse cultural and linguistic settings.