This article deals with Triple Helix (university, industry and government cooperation) from an institutional theory perspective. The empirical context is the Western Cape Region in South Africa and the focus is entrepreneurship development. The purpose is two-fold: first, the existing Triple Helix model is adapted to the South African context; and second, facilities and impediments for working according to Triple Helix in South Africa are identified. The empirical material consists of a survey and three longitudinal case studies illustrating the degree of cooperation between the three parties. The article contributes to knowledge about how the Triple Helix model works on a regional level in a developing country. The study draws the following conclusions: when cooperation is to be identified between the three actors, only two of the three are involved; one missing link in the Triple Helix model is the focus on the entrepreneur; cooperation between the three parties are incidental rather than planned and there is lack of structure. In turn, some of these conclusions may be an effect of institutional changes on a national level. For a normative legacy, the article proposes a set of suggestions for incorporating all relevant parties on a practical level.