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This study aims to clarify any association between infant birth weight and cannabis use in pregnancy based on urine drug screens.A retrospective medical record review of singleton births from August 2013 through December 2014 with available urine drug screens (UDS) at initiation of prenatal care and delivery was conducted at a large tertiary academic referral center. Patients who used drugs other than cannabis were excluded.The prevalence of cannabis use in pregnancies not complicated by use of other drugs as evidenced by tetrahydrocannabinol in the urine of 2173 patients was 22.6%. Infants born to mothers who tested positive for only tetrahydrocannabinol in urine at both presentation for prenatal care and delivery were of lower median birth weight compared with those who tested negative [2925 g (IQR 2522–3265) vs 3235 g (IQR 2900–3591), P = <0.001]. There was no clinically relevant difference in gestational age at birth [39.0 weeks (IQR 37.1–40.0) vs 39.3 weeks (IQR 38.3–40.0), P = 0.012] between those positive for tetrahydrocannabinol (THC) and those who tested negative. Concomitant tobacco use during pregnancy was not noted to impact infant birth weight using the analysis of covariance. Higher perinatal mortality was observed among those who used cannabis with an adjusted odds ratio of 4.2 (95% CI, 1.53–11.49).Cannabis use is negatively correlated with fetal birth weight (up to 450 g less) in patients who tested positive for THC when compared with those who did not as documented in the urine drug screens. On the basis of these findings, additional patient education and cessation interventions should be explored with regard to cannabis use in pregnancy.