OBJECTIVE: Array CGH is transforming clinical cytogenetics with its ability to interrogate the human genome at increasingly high resolution. To determine whether array CGH testing in the prenatal population provides diagnostic information over conventional karyotyping. METHODS: MEDLINE (1970-Dec 2009), EMBASE (1980-Dec 2009), and CINAHL (1982-Dec 2009) were searched electronically. Studies were selected if array CGH was used on prenatal samples or where array CGH was used on postnatal samples following termination of pregnancy for structural abnormalities detected on an ultrasound. Of the 135 potential articles, ten were included in this systematic review and eight in the meta-analysis. The pooled rate of extra information detected by array CGH when the prenatal karyotype was normal was meta-analysed using random effects model. The pooled rate of receiving an array CGH result of unknown significance was also meta-analysed. RESULTS: Array CGH detected 3.67% (95% CI 1.5 - 8.5%) additional genomic imbalances when conventional karyotyping was "normal" regardless of referral indication. This increased to 5.2% (95% CI 1.9 -13.9%) more than karyotyping when the referral indication was a structural malformation on ultrasound. CONCLUSIONS: There appears to be an increased detection rate of chromosomal imbalances when array CGH techniques are employed in the prenatal population over conventional karyotyping. However, some are copy number imbalances that are not clinically significant. This carries implications for prenatal counselling and maternal anxiety. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.