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Nigeria’s battle against HIV/AIDS faces multifaceted challenges, with various barriers critically impacting the effectiveness of control efforts. Employing Ostrom’s Institutional Analysis and Development (IAD) framework, this qualitative study examines key obstacles hindering the success of interventions. Through a combination of document analysis and thematic analysis of secondary data sources, the research reveals institutional barriers such as contradictory legislation, underutilization of allocated resources, insufficient domestic funding, harmful cultural practices, and inadequate monitoring and evaluation. While previous studies have highlighted the impact of HIV/AIDS on Nigeria’s health system, society, and economy, this study fills a gap by focusing on the institutional context that shapes the success of interventions. The findings contribute to the evidence base on the institutional dimensions of HIV/AIDS control in Nigeria and suggest a systems-oriented approach, participatory governance, and evidence-based implementation as potential strategies to address institutional challenges and optimize the impact of control efforts.