This study investigated the relationship between vocabulary knowledge (written and aural receptive vocabulary size and self-rating of vocabulary knowledge) and self-perceptions of four language skills (reading, listening, writing, speaking) targeting undergraduate students in English-medium instruction (EMI) courses in Japan. The students' academic performance (course grades and quiz scores) was also compared to their vocabulary knowledge. Results showed that learners with larger aural vocabulary sizes were more confident in spoken language use, and those who self-rated higher on their vocabulary knowledge were more likely to perceive themselves as proficient in productive language skills. Interestingly, learners with larger written vocabulary sizes tended to perceive themselves as less proficient in performing EMI tasks. Results also showed that none of the vocabulary measures were significantly associated with academic outcomes. Interview data suggest that EMI students' performance could be affected by the complex interplay of various factors, though not necessarily a large vocabulary size alone. Based on these findings, implications are discussed in terms of teaching and assessing vocabulary knowledge in EMI courses.