Information systems (IS) are complex phenomena. For instance, the diffusion of IS in small and medium enterprises (SMEs) depends on various levels of networked, localized, and changing determinants, such as the ones related to the adopter organizations, decision makers, technologies, complementary innovations, business partners, professional groups, universities, and government policies. This complex view of IS implies the use of different disciplines and methodologies to study the diffusion process. The objective of this empirical research is to demon strate how the systems of innovation approach (SIA), for addressing the institutional and evolutionary determinants of diffusion, and the philosophical stance of critical realism (CR), for guiding the research process, are compatible and meet the multidisciplinarity and methodological pluralism required to move on the field of complex IS and recommend meaningful actions to practice. To exemplify our arguments, we focus the study on one relevant determinant that affects the diffusion of IS in SMEs, namely government programs.