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The primary purpose of this study was to assess the effects of contextually-based multiple meaning (i.e., words with multiple meanings) vocabulary instruction on the vocabulary knowledge and reading comprehension of students. Third and 5th grade students received either contextually-based multiple meaning vocabulary instruction embedded in the standard language arts instruction offered to all students over a three-month period or the standard language arts instruction alone (i.e., non-specific treatment). Students who received the contextually-based multiple meaning instruction generally showed statistically and educationally significant gains in their vocabulary knowledge and reading comprehension relative to students who did not. These gains were most evident in reading comprehension. Additionally, students with low initial vocabulary knowledge and reading comprehension achievement tended to show greater gains than those with average to high achievement. These effects were more pronounced in the case of 3rd grade students. The results and limitations are discussed.