This experimental study examined the efficacy of a multicomponent reading intervention compared to a business-as-usual comparison condition on the reading comprehension and content area vocabulary outcomes of adolescent students with low reading comprehension. We randomly assigned 9th-grade students with low reading comprehension to a researcher-provided intervention (n = 51) or a business-as-usual comparison (n = 49) group. Reading interventionists provided weekly instruction for 2 semesters (M = 114 hr) to small groups of students (M = 5). We estimated intervention effects for each outcome measure using repeated measures analyses of covariance (ANCOVAs) for measures of reading and vocabulary. Results indicated statistically significant differences between students in the intervention and comparison conditions on measures of vocabulary and on the Test of Sentence Reading Efficiency and Comprehension (TOSREC) and no differences on the Woodcock–Johnson III Passage Comprehension subtest. Repeated measures ANCOVAs indicated large effect sizes on vocabulary measures between intervention and comparison students on multiple-choice and free response items (η p2 =.16 and.19, respectively) and small effect sizes on the TOSREC (η p2 =.02).