Objectives/Goals: Second-generation antipsychotics (SGA) are used to treat mental disorders in youth but are linked metabolic syndrome (MetS). Most data on prescribing practices and risk factors are from short-term studies (6–12 months). We aim to characterize prescribing and identify clinical and genetic predictors of MetS using electronic health records (EHR). Methods/Study Population: EHR data were extracted from Cincinnati Children’s Hospital Medical Center (CCHMC) for patients aged ≤21 years prescribed SGAs from 7/1/2009 and 7/1/2024, identifying prescribing prevalence. Next steps are to create an SGA-MetS case–control dataset 8 weeks after an SGA prescription. A case will be defined by meeting 3 of 5 criteria: 1) BMI ≥95th percentile for age/sex; 2) fasting glucose ≥100 mg/dL or use of anti-diabetics; 3) triglycerides ≥110 mg/dL; 4) HDL-C ≤40 mg/dL; 5) systolic/diastolic BP ≥90th percentile for age/sex or use of antihypertensives. The prevalence of SGA-MetS will be calculated by dividing SGA-MetS cases by total SGA users. Logistic regression will identify clinical predictors of MetS, and we will evaluate the association of polygenic risk scores (PRS) of BMI and type 2 diabetes with SGA-MetS risk. Results/Anticipated Results: Our preliminary analysis identified 30,076 patients who were prescribed SGAs (mean age 12 years, SD = 4; 58.8% female; n =  17685). Most self-identified as non-Hispanic (95%, n = 28,595) and of White race (76%; n =  22,935), with 18.5% self-identifying as Black or African American (n = 5,579). The most commonly prescribed SGAs were risperidone (n = 12,382, 41.1%), aripiprazole (n = 9,847, 32.7%), and quetiapine (n = 5,263, 17.5%), with much lower prescribing rates of other SGA known of their low risk of MetS (e.g., ziprasidone 5.5%, lurasidone 1.4%, paliperidone (n = 316, 1.1%), or others cariprazine (n = 72), asenapine (n = 43), brexipiprazole (n = 39), iloperidone (n = 24), and clozapine (n = 20). Discussion/Significance of Impact: Our analyses found that risperidone, quetiapine, and aripiprazole were the most prescribed SGA, with risperidone/quetiapine linked to a higher risk of MetS. We will present ongoing work identifying risk factors for SGA-MetS and examining the association with PRS. Our work has the potential to identify high-risk patients for personalized treatment.