Objective: To examine the real world impact of antipsychotics on weight gain in adolescent patients (12-19 years) taking second-generation (SGA) or first-generation antipsychotics (FGA). Methods: Naïve monotherapy patients receiving FGA's or SGA's between July 1999 and March 2006 were identified using the GE Centricity electronic medical record database; patients on clozapine or depot antipsychotics were excluded. Baseline Body Mass Index (BMI) recorded within =90 days prior and closest to index prescription date was compared with maximum BMI obtained during the follow-up period (at least 90 days to end of study period or monotherapy period). Multivariate linear and logistic regressions were conducted to estimate the magnitude of weight gain and odds of 5%, 10%, 15%, and 20% increase in BMI. To account for growth, BMI was normalized by calculating z-scores and odds of =0.5 change in baseline to follow-up z-scores were estimated. Results: A total of 1179 eligible patients were identified with mean age 15.2 years (SD, 2.16) and 51% female. The distribution was: FGA's 19% (n=253), aripiprazole 11% (n=129), olanzapine 15% (n=182), quetiapine 25% (n=297), risperidone 26% (n=308), and ziprasidone 3% (n=32). In the linear model, adolescents on olanzapine experienced a significant increase in BMI [0.84 kg/m2 (CI, 0.17-1.52)] compared to those on aripiprazole. Logistic model results indicated a significant likelihood of a 5 to 20% increase in BMI for those on olanzapine [OR: 1.54 (CI, 0.96-2.5) to 4.53 (CI, 1.79-11.48) and a 10 to 20% increase for those on risperidone [OR: 1.84 (CI, 1.15-3.0) to 2.18 (CI, 1.21-3.96)], compared to aripiprazole. In the BMI z-score analysis, adolescents on olanzapine experienced a significant increase in BMI [OR: 1.65 (CI, 1.02-2.67)]. Results for FGA's, quetiapine, and ziprasidone were not statistically significant. Conclusion: Potential for weight gain varies by antipsychotics and should be taken into account while prescribing these medications to adolescents.