The adoption of methods and strategies validated through rigorous, experimentally oriented research is a core professional value of special education. We conducted a systematic review and meta-analysis examining the experimental literature on Technology-Aided Instruction and Intervention (TAII) using research identified as part of the National Autism Professional Development Project. We applied novel between-case effect size methods to the TAII single-case research base. In addition, we used meta-analytic methodologies to examine the methodological quality of the research, calculate average effect sizes to quantify the level of evidence for TAII, and compare effect sizes across single-case and group-based experimental research. Results identified one category of TAII—computer-assisted instruction—as an evidence-based practice across both single-case and group studies. The remaining two categories of TAII—augmentative and alternative communication and virtual reality—were not identified as evidence-based using What Works Clearinghouse summary ratings.