The growth of English medium instruction (EMI) programs at universities worldwide has raised questions about the implications of teaching through L2 English on students' content learning outcomes. This study examined the impact of four factors on students' academic success (e.g. content learning) in the Turkish EMI context: (1) students' language-related challenges; (2) students' opinions about the effectiveness of EMI; (3) students' perceived language proficiency levels; and (4) the amount of L2 English used in EMI classes. Students' perceived academic performance was taken as a proxy of EMI success. The study employed a quantitative empirical design using questionnaires and regression analysis. Data were collected via an online questionnaire from 498 students at an EMI university in Turkey. The results revealed that students' language-related challenges and perceived language proficiency were the only predictors that were associated with academic success in their EMI courses at a statistically significant level. The amount of English used in the classroom was not found to predict success in EMI, suggesting that students may benefit from multilingual models of teaching. These findings underscore the importance of adequate language support for students on EMI programs, and implications are discussed with respect to EMI policy, program planning, and teacher pedagogy.