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The American Academy of Pediatrics recommends pre-discharge Car Seat Tolerance Screening (CSTS) for all neonates born37 weeks estimated gestational age (EGA), or otherwise at risk for cardiorespiratory compromise. Screening is burdensome and there remains tremendous variation in testing criteria and methodology.We conducted a retrospective chart review of 1,072 infants who underwent CSTS between 11/2013 and 7/2016 at a single academic health center. CSTS outcomes (failure and, separately, significant cardiorespiratory instability (CRI)), including those not meeting failure thresholds) were analyzed for all infants screened, and for preterm infants by screening location (Neonatal Intensive Care Unit (NICU) and Mother/Baby Unit (MBU)). Logistic regression was used to estimate associations between infant characteristics and CSTS outcomes.Overall incidence of CSTS failure was 9.2%. Among all infants, hemodynamically significant congenital heart disease, apnea, chronic lung disease, and being small for EGA were associated with failure. Additionally, those born ≤28 weeks EGA had 2.4 times greater likelihood of failure than those 34-36 weeks EGA. Among preterm infants in the NICU and MBU, those of earlier EGA were also more likely to fail. Almost half (47.5%) of all preterm infants demonstrated CRI during CSTS.We found high CSTS failure rates, and identified key infant characteristics that were associated with increased likelihood of failure. Significant CRI events were remarkably common. Larger, prospective studies are needed to elucidate risk factors for instability and failure and define practical criteria for CSTS recommendations.