The scope of this study was to evaluate whether the adoption of e-learning in two universities, and in particular, the relationship between the perception of external control and perceived ease of use, is different because of gender differences. The study was carried out with participating students in two different universities, one in Chile and one in Spain. The Technology Acceptance Model was used as a theoretical framework for the study. A multi-group analysis method in partial least squares was employed to relate differences between groups. The four main conclusions of the study are: (1) a version of the Technology Acceptance Model has been successfully used to explain the process of adoption of e-learning at an undergraduate level of study; (2) the finding of a strong and significant relationship between perception of external control and perception of ease of use of the e-learning platform; (3) a significant relationship between perceived enjoyment and perceived ease of use and between results demonstrability and perceived usefulness is found; (4) the study indicates a few statistically significant differences between males and females when adopting an e-learning platform, according to the tested model.