Reading comprehension is a critical skill for school success. Struggling readers can benefit from computer-assisted instruction that utilizes components of effective instruction (e.g., frequent practice, immediate feedback). The purpose of this study was to examine the effects of Headsprout Comprehension, a computer-assisted reading program, on the reading comprehension of six elementary students with high-incidence disabilities (i.e., learning disabilities, emotional disturbance, and other health impairment–attention deficit hyperactivity disorder (OHI-ADHD). A multiple baseline across participants’ design demonstrated that Headsprout Comprehension was functionally related to substantial increases in reading comprehension for all six participants as measured by Ohio Achievement Assessment (OAA) passage comprehension questions and AIMSweb Maze assessments.