Background: Avoidable hospital readmission is a major problem among health systems. Although there are effective peri-discharge interventions for reducing avoidable hospital readmission, successful implementation is challenging. This systematic review of qualitative studies aimed to identify barriers and facilitators to implementing peri-discharge interventions from providers’ and service users’ perspectives. Methods: We searched four databases for potentially eligible qualitative studies from databases’ inception to March 2020, and updated literature search for studies published between January 2020 to October 2021. Barriers and facilitators to implementing peri-discharge interventions were identified and mapped onto the Consolidated Framework for Implementation Research (CFIR) constructs. Inductive analysis of the CFIR constructs was performed to yield thematic areas that illustrated the relationship between various facilitators and barriers, generating practical insights to key implementation issues. Results: Thirteen qualitative studies were included in this systematic review. Key issues were clustered in the CFIR constructs of Design Quality and Complexity of the intervention, strength of Network and Communication, being responsive to Patient Needs with sufficient Resource support, and External Incentives. The three thematic areas were rationality of the interventions, readiness and effort of multidisciplinary implementation teams, and influence of external stakeholders. Common barriers included (i) limited resources, (ii) poor communication among team members, (iii) incompatibility between the new intervention and existing work routine, (iv) complicated implementation process, (v) low practicality of supporting instruments, and (vi) lack of understanding about the content and effectiveness of the new interventions. Common facilitators were (i) information sharing via regular meetings on implementation issues, (ii) organizational culture that values quality and accountability, (iii) financial penalties for hospitals with high avoidable readmissions rates, (iv) external support offered via quality improvement programs and community resources, and (v) senior leadership support. Conclusion: This study synthesized commonly-presenting barriers and facilitators to implementing peri-discharge interventions among different healthcare organizations. Findings may inform development of implementation strategies in different health systems after appropriate tailoring, based on a consensus-based formative research process.