The purpose of this study was to synthesize the effectiveness of computer-assisted instruction (CAI) studies aiming to increase vocabulary for students with disabilities in an effort to identify what type of CAI is promising for practice. An extensive search process with inclusion and exclusion criteria yielded a total of 13 single-subject design studies to be included in the present study. Effect sizes were calculated using a percentage of nonoverlapping data (PND). We also analysed instructional features (e.g., visual supports, auditory supports, font/color selection, and corrective and interactive feedback) from the studies that examined effective instructional design features of CAI. Results indicated (a) the highest PND mean was for secondary school-aged learners with disabilities; (b) both tablet-assisted instructions and nontablet-assisted instruction produced high PND (i.e., highly effective); and (c) although the majority of selected studies included visual and auditory supports in CAI for vocabulary, none of the studies provided opportunities for customization (e.g., student selection of colors and fonts). On the basis of the findings, implications for future research and practice are discussed.