Asymmetric crying face (ACF) is a minor anomaly found in 3-8 per 1,000 births, which may be associated with other anomalies. Previous studies on this topic included small groups of selected subjects, resulting in large variations in findings. The aim of this study was to examine the characteristics and associated anomalies of newborn infants with ACF compared with the general population of newborn infants. The study included newborn infants delivered between 1993 and 2003 at the Department of Neonatology of Rabin Medical Center, Israel. Charts of all newborns diagnosed with ACF were reviewed for obstetric and neonatal details, then compared with non-ACF newborns. ACF was diagnosed in 258 of 67,289 newborns (0.38%), with left-side predominance (77%). Major malformations were found in 7% of ACF infants, 3.5-fold higher than in the total Israeli population. Mild anomalies were present in 15% of the ACF group, and deformations in 4.6%. There was a higher rate of forceps deliveries in the ACF group (RR = 2.73, 95% CI = 1.37-5.42). ACF was more prevalent among females, and the male:female ratio was lower in the ACF group (0.86 vs. 1.06, P = 0.05). The rate of low-birth-weight infants was 3.9% among ACF infants and 9.6% in the control group (RR = 0.41, 95% CI = 0.23-0.76). No significant between-group difference was found for rates of primiparity, macrosomia, prematurity, postmaturity, or size-for-gestational-age. Thus, ACF is associated with a high rate of major malformations. This should prompt clinicians to seek for additional birth defects in ACF infants.