An inferential comprehension intervention addressing reading comprehension difficulties of middle schoolers was tested. Method Students in Grades 6 to 8 (n = 145; 53.8% female; 71% White; 24% Black) who failed their state literacy test, were randomly assigned to tutor-led, computerized, or business-as-usual [BaU] interventions. Results The tutor-led intervention produced significant effects compared to BaU (g = 0.40) and computer-led (g = 0.30) on inference types instructed in the intervention. Students with adequate word reading in tutor-led gained more compared to BaU on WIAT-III Reading Comprehension. Boys gained more from tutor-led and BaU vs. computer-led on several measures. Conclusion Inferential comprehension is malleable in middle school, but adequate word reading may be important. The effects for boys vs. girls suggest the need to understand intervention factors beyond the content and instructional procedures of interventions. Findings are discussed with reference to theories of inference and reading comprehension as well as the literature on technology-aided literacy interventions.