This study aimed to explore the role of inference making in the relation between vocabulary knowledge (breadth and depth) and reading comprehension for 487 ninth-grade Chinese EFL students who were categorized as either struggling or adequate. Path analysis was used to examine both direct and mediated effects. The results indicated a statistically significant indirect effect of vocabulary knowledge on reading comprehension, mediated by inference making, for the entire participant group. However, there were notable differences between the struggling and adequate readers, as evidenced by distinct path diagrams. For struggling readers, the indirect effect of vocabulary breadth on reading comprehension through inference making was significant, while that of vocabulary depth was not significant. For adequate readers, both vocabulary breadth and depth directly explained reading comprehension. These results are discussed in the EFL context, encompassing assessment and instructional implications for EFL readers with varying levels of reading abilities.