This U.S. study evaluated the effects of a reading intervention for emergent bilingual students with significant reading difficulties in Grades 6 and 7 within a multisite randomized controlled trial. Emergent bilinguals were randomized to a researcher-provided intervention (n = 171) or business-as-usual comparison condition (n = 169). Results on a measure of word reading indicated significant differences favoring treatment after Year 1; however, there were no significant differences between groups on standardized measures of reading comprehension. Initial English vocabulary knowledge moderated reading comprehension scores at the beginning of the second year of intervention, indicating that students' response to instruction varied as a function of their initial English language proficiency. The discussion focuses on interpreting these findings with an emphasis on improving the effectiveness of interventions for secondary grade emergent bilinguals with significant reading difficulties.