The Caribbean region presents the highest prevalence of HIV/AIDS worldwide after sub-Saharan Africa; leading to serious social, economic and health consequences at the local scale but also at the regional and global levels. In Colombia, a national plan to tackle the epidemic was formulated with little evidence that its implementation in the local context is effective. This study focused on Cartagena - one of Colombia's largest cities and an international touristic hub - that presents one of the highest HIV prevalences in the country, to investigate whether the national plan accounts for local specificities and what are the barriers to local implementation. Based on the Contextual Interaction Theory (CIT), this qualitative research relied upon 27 interviews and 13 life stories of local inhabitants and stakeholders, collected in a first fieldwork in 2006-2007. A follow-up data collection took place in 2013 with 10 participants: key policymakers and implementers, NGO representatives and local inhabitants. Barriers identified by the participants included: local population's understandings and beliefs on condom use; stigma and discrimination; lack of collaboration from the Church, the education sector and local politicians; corruption; high staff turnover; frequent changes in leadership; lack of economic and human resources; and barriers to health care access. The findings suggest that global influences also have an impact on the CIT framework (e.g. international organisations as a major financier in HIV prevention). The participants put forward several feasible solutions to implementation barriers. We discuss how several of the proposed solutions have been applied in other Latin American and Caribbean countries and yielded positive results. However, further research is needed to find possible ways of overcoming certain barriers identified by this study such as corruption, the lack of collaboration of the Church and barriers to health care access.