Previous research has documented that students' reading comprehension performance in learning English as a foreign language (EFL) differs greatly between mobile-assisted and paper-based reading. The present study extends previous work by investigating whether reading cognitive load differs between mobile-assisted and paper-based EFL reading processes and exploring whether cognitive load mediates the relationship between reading medium and EFL reading comprehension performance. The instruments used are reading comprehension tests and questionnaire surveys administered to a sample of 191 first-year college students. A repeated-measures analysis of variance (ANOVA) indicates that cognitive load is significantly greater for mobile-assisted EFL reading than for paper-based EFL reading. In addition, structural equation modeling analyses indicate that cognitive load fully mediates the relationships between medium and reading comprehension performance; these mediation effects are independent of the level of English language proficiency. These results imply that cognitive load is a pivotal factor influencing students' reading comprehension across media. Reasons for differences in reading cognitive load and its role as a mediator are discussed. Recommendations for promoting students' reading experience on mobile phones are provided.