Rates of neonatal abstinence syndrome (NAS) have increased fivefold in the past decade. To address this expanding and complex issue, state public health agencies have addressed the opioid crisis affecting newborns in diverse ways, leading to a variety of methods to quantify the burden of NAS.In an effort to understand this variability, we summarized clinical case and surveillance definitions used across jurisdictions in the United States. We confirmed that the rapid progression of the nation's opioid crisis resulted in heterogeneous processes for identifying NAS. Current clinical case definitions use different combinations of clinician-observed signs of withdrawal and evidence of perinatal substance exposure. Similarly, there is discordance in diagnosis codes used in surveillance definitions. This variability makes it difficult to produce comparable estimates across jurisdictions, which are needed to effectively guide public health strategies and interventions.Although standardization is complicated, consistent NAS definitions would increase comparability of NAS estimates across the nation and would better guide prevention and treatment efforts for women and their infants.