OBJECTIVE: The aim of this study was to examine the effect of Key Word Sign (KWS) intervention on the acquisition and generalization of manual signing among three children with Autism Spectrum Disorder (ASD), and to measure any changes in their production of spoken words and gestures following intervention. METHODS: A multiple baseline single-case experimental design was used to measure changes for each of the three children. RESULTS: All three children began using signs following the introduction of the KWS intervention, and generalized their use of some signs across activities. The introduction of the intervention was associated with either neutral, or statistically significantly positive, changes in the children's production of spoken words and natural gestures. CONCLUSION: The results provide preliminary evidence for the effectiveness of KWS for preschool children with ASD, which parents, therapists, and educators can use to inform clinical practice.