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Background: Post-acute coronary syndrome (ACS) depression is a common but not well understood complication experienced by ACS patients. Research on the effectiveness of various therapies remains limited. Hence, we sought to conduct a network meta-analysis to assess the efficacy of different interventions for post-ACS depression in improving patient outcomes., Methods and Findings: Three electronic databases were searched for randomised controlled trials describing different depression treatment modalities in post-ACS patients. Each article was screened based on inclusion criteria and relevant data were extracted. A bivariate analysis and a network meta-analysis was performed using risk ratios (RR) and standardized mean differences (SMD) for binary and continuous outcomes, respectively. A total of 30 articles were included in our analysis. Compared to standard care, psychosocial therapy was associated with the greatest reduction in depression scores (SMD:-1.21, 95% CI: -1.81 to -0.61, p<0.001), followed by cognitive behavioural therapy (CBT) (SMD: -0.75, 95% CI: -0.99 to -0.52, p<0.001), antidepressants (SMD: -0.73, 95% CI: -1.14 to -0.31, p<0.001), and lastly, combination therapy (SMD: -0.15, 95% CI: -0.28 to -0.03, p = 0.016). No treatment modalities was found to be more effective in reducing depression scores when compared to one another. Additional analysis showed that these treatment modalities did not have significant impact on the overall mortality, cardiac mortality and recurrent myocardial infarction., Conclusion: This network meta-analysis found that the treatment effect of the various psychological modalities on depression severity were similar. Future trials on psychological interventions assessing clinical outcomes and improvement in adherence to ACS-specific interventions are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Lim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)