Although instruction has been shown to be effective at increasing vocabulary knowledge and comprehension, factors most important for promoting the acquisition of novel vocabulary are less known. In addition, few vocabulary studies have utilized models that simultaneously take into account child-level, word-level, and instructional factors to better understand the acquisition of novel vocabulary from informational text. Sixty-eight children with reading difficulties in Grades 3--5 were randomly assigned to either vocabulary strategy instruction or traditional comprehension instruction with both groups reading the same set of expository texts. Crossed random-effects models were used to predict item-level variance in vocabulary acquisition. Results indicated main effects for condition favoring vocabulary instruction, child-level predictors (vocabulary and knowledge of the content), and word-level factors (frequency and imageability). One interaction was significant, indicating that students with higher vocabulary scores were more likely to do better when provided vocabulary instruction than students with lower prior vocabulary.