Against the backdrop of internationalisation of education and the emergence of English as a global language, medium of instruction (MOI) has long been a controversial issue globally. The present study examined the relationships between secondary-level MOI (English, EMI; Chinese, CMI) and learners' tertiary-level academic achievement and perceptions. 434 tertiary-level business, science, and social science students in Hong Kong completed a survey and 18 of them also attended an interview. An overall significant difference was found in tertiary-level academic achievement between the EMI and CMI students. Significant differences were also found in their self-rated performance in and preferences for some but not all kinds of assessments. When analysed by tertiary-level disciplines, business students showed no differences while science students showed some, and social science students showed the greatest differences between the CMI and EMI groups. The interviewees highlighted academic and psychological challenges facing CMI students. Implications for educators and researchers are discussed.