Introduction The regional Board of Health in Stockholm, Sweden, established the Pharmacotherapy Centre (PTC) to enhance the rational use of medicines. The PTC initiated computerised decision support systems and developed a range of electronic service products to sustain rational prescribing. However, knowledge about which determinants have supported or hindered the sustainability of this type of healthcare organisation is limited. Objective This study aims to identify and explore determinants that support or challenge the development and sustainability of the PTC organisation, as well as investigate the key elements of their implementation efforts. Methods An in‐depth interview study among key informants involved in the establishment of the PTC organisation was conducted. Data were analysed using qualitative content analysis. Results Findings suggest that determinants enabling the development and expansion of this organisation include the presence of innovative characteristics among the PTC leadership and the ability of leaders to nurture visionary innovation in others, as well as the instigation of informal social networks and to identify end‐user needs. Challenges included an ambiguous relationship to the pharmaceutical industry, an underestimation of the innovation‐system fit and to undertake systematic evaluation of created impact by the organisation. Although prescriber use of electronic service products and adherence to an essential drug list increased over time, it remains difficult to identify methods required for demonstrating patient effects. Conclusion Whereas some determinants enabled the successful expansion of the PTC organisation, others served to substantially hinder it. The determinants identified can pave the way for systematic investigations into organisational change and development research in the pharmaceutical field. Copyright © 2013 John Wiley & Sons, Ltd.