Abstract: The aim of this paper is to study differences in the adoption of e-commerce associated with the level of managers/owners’ innovativeness. The background utilized to estimate the respondents’ favorable reception of e-commerce is a model based on the Theory of Planned Behavior, which has been extended to include perceived drivers and obstacles as antecedents of attitude toward e-commerce acceptance. Small and medium enterprises in Chile participated in the study. A Partial Least Squares multi-group test was employed to note differences between groups. The main conclusions of the study are: (1) the level of managers/owners’ innovativeness differentiates between adopters and non-adopters of e-commerce of small and medium enterprises in Chile; (2) the Theory of Planned Behavior has been successfully used to explain the process of adoption of e-commerce among Chilean managers/owners; (3) there are significant relationships between both drivers and obstacles and attitude toward using e-commerce; (4) a strong and significant relationship exists between attitude and intention to use e-commerce. Results can be used by small and medium enterprises in developing countries to boost e-commerce adoption.