Trisomy 21, the chromosomal condition responsible for Down syndrome (DS, OMIM #190685), is the most common identifiable genetic cause of intellectual disability. Approximately half of all children with DS are born with a significant congenital heart defect (CHD), the most common of which is an atrioventricular septal defect (AVSD). As children with comorbid DS and CHD increasingly survive cardiac surgery, characterization of their early developmental trajectories is critical for designing early interventions to maximize individual potential. Herein, the developmental domains (cognitive, language, and motor) of children with DS and AVSD (DS + AVSD, n = 12) were compared to children with DS and a structurally normal heart (DS − CHD, n = 17) using the Bayley Scales of Infant and Toddler Development III. The DS + AVSD cohort mean age was relatively the same as controls with DS − CHD, 14.5 ± 7.3 months compared with 14.1 ± 8.4 months, respectively. Although the motor domain was the only domain that showed a statistically significant difference between groups (P < 0.05), both cognitive standard scores (P = 0.63) and language composite standard scores (P = 0.10) were lower in the DS + AVSD cases compared with the DS − CHD controls although it is not statistically significant. Since this is the first study to examine the early developmental outcomes of children with DS + AVSD, the findings may be useful for clinicians in providing anticipatory guidance. © 2011 Wiley Periodicals, Inc.