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This study was designed to assess the relative contributions of vocabulary and syntactic knowledge as predictors of reading comprehension performance. It also sought to investigate the interrelationship between syntactic and word knowledge and reading comprehension performance. Participants included 159 male freshman and sophomore Iranian high school students. Data were collected through the reading section of a retired version of Preliminary English Test (2004), Vocabulary Levels Test, Word Associates Test, and Syntactic Knowledge Test. The results revealed that both grammar and vocabulary scores correlated positively with reading comprehension scores. Also, vocabulary correlated significantly with reading comprehension but not as strongly as syntactic knowledge did. Our analysis revealed that syntax explains a larger portion of the reading variance. To examine whether depth / breadth of vocabulary knowledge or syntax may have more predictive power in reading comprehension performance, multiple-regression analysis was conducted. Beta values indicated that grammar made statistically significant contribution to reading comprehension, although other variables explained the variance on the reading test. The results offer new insights into the significant mediating influence that learner’s knowledge of grammar may have in reading comprehension at low intermediate level.