Fifty-five students with intractable epilepsy and learning difficulties, aged 6.5 to 14.1 years with a mean IQ of 71.25 (SD=13.56), attended a hospital-based classroom of no more than eight students where they received Direct Instruction programming for 3 to 4.5 days a week, typically for up to 16 weeks. Pretest–posttest academic gains were evaluated in comparison to normative test performance. At pretest the students were achieving below test means in reading and mathematics, particularly in calculation. Direct Instruction was associated with significant improvement in all academic areas except word identification in reading. IQ level was related to certain academic gains, but gains were not associated with seizure variables or the number of days students spent in the program. Despite severe learning difficulties, students with intractable epilepsy can make academic gains when taught by highly structured teaching methods such as Direct Instruction.