This study examines whether explicit reading comprehension instruction is relevant for students with high-functioning autism spectrum disorder (ASD). Forty-five students (M[subscript age] = 9 years) were randomly assigned to two conditions: control or intervention. Those assigned to the intervention condition received instruction on vocabulary, main idea identification, text structure, and anaphoric relations. Compared with their peers in the control condition, students in the intervention condition showed greater improvement on one measure of reading comprehension. They also knew the meaning of more words and were better able to identify main ideas and anaphoric relations, with some of these gains still being detectable at the follow-up. Although additional adaptations appear warranted, students with high-functioning ASD clearly benefited from instruction.