Strong vocabulary knowledge is important for success in reading comprehension for English language learners (ELLs). The interplay between first (L1) and second language (L2) vocabulary knowledge in L2 English reading comprehension was examined to determine whether ELLs, whose command of L1 and L2 vocabulary varied across languages, differed in English reading comprehension in grades 2 and 4. ELLs (n = 105) were assigned to a bilingual profile group based on their L1 and L2 vocabulary knowledge and in relation to the sample: L1 dominant (strong L1), L2 dominant (strong L2), high balanced (strong in both), or low balanced (compromised in both). Relationships among L1 and L2 (English) vocabulary, nonverbal cognitive ability, word reading, and reading comprehension in English were examined. Results indicated that reading comprehension was related to bilingual profile, and that a three group model better characterized the sample when compared to the four group model that was initially hypothesized. L1 vocabulary was not uniquely predictive of L2 (English) reading comprehension. L2 vocabulary aligned betterwith reading comprehension concurrently in grade 2, and longitudinally in grade 4. In support of a common underlying cognitive processes perspective, individual differences in learning vocabulary may be a proxy forgeneral language learning ability, which supports reading comprehension.