Background: Disease management programmes are increasingly used to improve the efficacy and effectiveness of chronic care delivery.But, disease management programme development and implementation is a complex undertaking that requires effective decision-making.Choices made in the earliest phases of programme development are crucial, as they ultimately impact costs, outcomes and sustainability.Methods: To increase our understanding of the choices that primary healthcare practices face when implementing such programmes and to stimulate successful implementation and sustainability, we compared the early implementation of eight cardiovascular disease management programmes initiated and managed by healthcare practices in various regions of the Netherlands. Using a mixed-methods design, we identified differences in and challenges to programme implementation in terms of context, patient characteristics, disease management level, healthcare utilisation costs, development costs and health-related quality of life.Results: Shifting to a multidisciplinary, patient-centred care pathway approach to disease management is demanding for organisations, professionals and patients, and is especially vulnerable when sustainable change is the goal. Funding is an important barrier to sustainable implementation of cardiovascular disease management programmes, although development costs of the individual programmes varied considerably in relation to the length of the development period. The large number of professionals involved in combination with duration of programme development was the largest cost drivers. While Information and Communication Technology systems to support the new care pathways did not directly contribute to higher costs, delays in implementation indirectly did.Conclusions: Developing and implementing cardiovascular disease management programmes is time-consuming and challenging. Multidisciplinary, patient-centred care demands multifaceted changes in routine care. As care pathways become more complex, they also ...