English-medium instruction (EMI) is considered to be one of the main instruments to internationalize universities all over the world. Due to its recent implementation, research on linguistic outcomes is on the increase, whereas non-linguistic outcomes have been neglected. In fact, research on motivation in traditional English as a foreign language context is abundant but it is remarkably scant in EMI settings, that is, studies focused on motivation when English is used to teach content are much less habitual than when English is taught as a foreign language (language subject). To fill this gap, this article focuses on the relationship between EMI, motivation and possible selves, and how they are mediated by variables such as gender and students' L1. Thus, this study elicits aspects overlooked by motivational self-system research such as students' motivation towards English as an L3 in an EMI context, as in previous studies English (L2) was taught as a foreign language. The participants in this study were 189 students enrolled in EMI courses at a Spanish university. The results indicated that students' ideal L2 self, their attitudes to EMI and family influence were the best predictors of their intended learning effort. The gender variable and the participants' L1 exerted no significant influence.