Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with macroglossia, abdominal wall defects, ear anomalies, and an increased risk for embryonic tumors. Reported tumor risk estimates vary between 4% and 21%. It has been hypothesized that tumor predisposition in BWS is related to the imprinting status of the H19 and LIT1 genes on chromosome 11p15. A loss of imprinting (LOI) of H19 implies a higher tumor risk. However, a systematic analysis of available data is lacking. Therefore, we performed a review and meta-analysis of reported associations between the imprinting status of the LIT1 and H19 genes and the risk for tumor development in BWS. Five publications suitable for meta-analysis were identified by electronic database searches. Sufficient data were available for 402 out of 520 patients. Patients were divided into four groups based on the imprinting status of H19 and LIT1: group I with LOI of LIT1 (45%); group II with LOI of H19 (9%); group III with LOI of LIT1 and LOI of H19 (21%); and group IV with normal imprinting patterns (26%). Differences in tumor risk between groups were studied with random effects meta-analysis. Tumors occurred in 55 patients. The odds of tumor development was significantly lower in group I when compared to group II (OR=0.06; 95% CI: 0.02-0.21) and group III (OR=0.12; 95% CI: 0.04-0.37). Tumor risk did not differ significantly between groups II and III (OR=1.40; 95% CI: 0.56-3.50). Compared to group IV, tumor risk was significantly lower in group I (OR=0.33; 95% CI: 0.12-0.87) and higher in groups II (OR=4.0; 95% CI: 1.5-10.4) and III (OR=2.6; 95% CI: 1.2-5.7). Tumor incidence rate for group IV was 10.6% (95% CI: 3.6-17.7). Calculated absolute risks were 3% for group I, 43% for group II, and 28% for group III, respectively. No Wilms tumor was seen in group I. In total, other tumors were seen with comparable frequencies in groups I-III. The results show a strong association between a LOI of H19 and especially Wilms tumor development in BWS.