To evaluate combined analysis with amniotic fluid index (AFI) and estimated fetal weight (EFW) for prediction of severe macrosomia at birth. In this retrospective case-control study, 50 term severe macrosomic newborns (birthweight [BW] > or = 97th percentile) were included in the study group and 100 appropriate for gestational age newborns served as controls. All pregnancies underwent a third-trimester sonographic evaluation in which AFI and EFW were measured. The association between BW and AFI and EFW percentiles was examined. The statistical analysis included Student t test, simple regression and receiver-operating curve analyses, and 2x2 tables. The mean mid-third-trimester AFI percentile and EFW percentile in severe macrosomic infants were 72.4 +/- 22.5 and 83 +/- 12, respectively, which was significantly higher than in controls (P < .0001). Significant correlations were detected between BW and AFI and EFW percentiles (r = 0.44 and r = 0.72, respectively; P < .0001). Receiver-operating characteristic analysis identified AFI > or = 60th percentile and EFW > or = 71st percentile as best predictors of severe macrosomia. The combined analysis with AFI > or = 60th percentile and EFW > or = 71st percentile resulted in a positive predictive value of 85%. There is a significant correlation between mid-third-trimester AFI and BW. AFI > or = 60th percentile and EFW > or = 71st percentile during the mid third trimester are useful predictors of severe macrosomia at birth.