The quality of staff/child interactions as measured by the Classroom Assessment Scoring System (CLASS) in Early Childhood Education and Care (ECEC) programs is thought to be important for children’s outcomes. The CLASS is made of three domains that assess Emotional Support, Classroom Organization and Instructional Support. It is a relatively new measure that is being used increasingly for research, quality monitoring/accountability and other applied purposes. Our objective was to evaluate the association between the CLASS and child outcomes. Searches of Medline, PsycINFO, ERIC, websites of large datasets and reference sections of all retrieved articles were conducted up to July 3, 2015. Studies that measured association between the CLASS and child outcomes for preschool-aged children who attended ECEC programs were included after screening by two independent reviewers. Searches and data extraction were conducted by two independent reviewers. Thirty-five studies were systematically reviewed of which 19 provided data for meta-analyses. Most studies had moderate to high risk of bias. Of the 14 meta-analyses we conducted, associations between Classroom Organization and Pencil Tapping and between Instructional Support and SSRS Social Skills were significant with pooled correlations of .06 and .09 respectively. All associations were in the expected direction. In the systematic review, significant correlations were reported mainly from one large dataset. Substantial heterogeneity in use of the CLASS, its dimensions, child outcomes and statistical measures was identified. Greater consistency in study methodology is urgently needed. Given the multitude of factors that impact child development it is encouraging that our analyses revealed some, although small, associations between the CLASS and children’s outcomes.