BACKGROUND: The spread of HIV and related infections are substantial in Northwest Russia. Interregional and intergovernmental bodies such as the Northern Dimension and the Barents Cooperation provides a framework for the cooperative efforts done in this area, while the implementation of activities is conducted by non-state actors on a regional or local level. AIMS: The central aim of this paper is to explore the aggregated efforts between Norway and the Russian Federation in combating HIV and AIDS in Northwest Russia. The objective is to identify the conditions of the cooperation, and examine under which of these conditions the outcome of the cooperation is successful. A state-centric and a governance perspective are applied to view the impact of central and horizontal structures, while institutional theory and regime theory are used to see conditions in an institutional and cooperative context. METHODS: This is a qualitative case-study of a Russian-Norwegian cooperative arrangement consisting of twelve projects between partner organizations in Norway and Russia dealing with HIV and AIDS in Northwest Russia. The data is retrieved from 109 project documents and seven semi-structured interviews with Norwegian project participants. RESULTS: The evidence indicates that there are two recurring themes, namely the role of actors and the institutional framework. The lower the level of the cooperation the easier it seems to create trust, whereas centralized decisions appear to tail out certain cooperative processes. Networks between and in-between Norwegian and Russian actors are significant in facilitating collaborative relations, while trust, respect and confidence are perceived as necessary and important for sustainable relations. Politicization creates certain cooperative difficulties, and there is an increased probability for politicization when dealing with issues of a controversial nature. Regional cooperation in the Northern area appears to function well when representatives from the Russian side are from the Northwestern regions. CONCLUSIONS: Managing to keep the cooperation efforts at a low governing level (locally or regionally), and avoiding politicization by distancing the efforts from sensitive politics, seems to increase the likelihood of success.