Purpose Speech production deficits and reduced intelligibility are frequently noted in individuals with Down syndrome (DS) and are attributed to a combination of several factors. This study reports acoustic data on vowel production in young adults with DS and relates these findings to perceptual analysis of speech intelligibility. Method Participants were eight young adults with DS as well as eight age- and gender-matched typically developing (TD) controls. Several different acoustic measures of vowel centralization and variability were applied to tokens of corner vowels (/ɑ/, /æ/, /i/, /u/) produced in common English words. Intelligibility was assessed for single-word productions of speakers with DS, by means of transcriptions from 14 adult listeners. Results Group differentiation was found for some, but not all, of the acoustic measures. Low vowels were more acoustically centralized and variable in speakers with DS than TD controls. Acoustic findings were associated with overall intelligibility scores. Vowel formant dispersion was the most sensitive measure in distinguishing DS and TD formant data. Conclusion Corner vowels are differentially affected in speakers with DS. The acoustic characterization of vowel production and its association with speech intelligibility scores within the DS group support the conclusion of motor control deficits in the overall speech impairment. Implications are discussed for effective treatment planning.