Objective: To evaluate 1) whether early nonresponse to antipsychotics predicts nonresponse and nonremission, 2) patient and illness characteristics as outcome predictors, and 3) response prediction of 30-item Positive and Negative Syndrome Scale (PANSS-30) compared with 6-item PANSS (PANSS-6) and Clinical Global Impressions–Improvement Scale (CGI-I) in youths with first-episode psychosis. Method: Post hoc analysis from a 12-week, double-blinded, randomized trial of aripiprazole vs extended-release quetiapine in adolescents (age 12-17 years) with first-episode psychosis was performed. Early nonresponse (week 2 or week 4) was defined as <20% symptom reduction (PANSS-30) (or <20% symptom reduction [PANSS-6] or CGI-I score 4-7 [less than “minimally improved”]). Nonresponse (week 12) was defined as <50% symptom reduction (PANSS-30). Nonremission (week 12) was defined as score ≤3 (mild) on 8 selected PANSS items. Positive/negative predictive values (PPV/NPV) and receiver operating characteristics, binary logistic regression models, and PPV/NPV using PANSS-6 and CGI-I were analyzed. Results: Of 113 randomized patients, 84 were included in post hoc analysis (mean [SD] age = 15.7 [1.3] years; 28.6% male). The 12-week symptom decrease was 31.9% [27.9%], most pronounced within the first 2 weeks (61.1% of total PANSS reduction). Response (27.4%) and remission (22.6%) rates were low. Results indicated that early nonresponse reliably predicted 12-week nonresponse (PPV: week 2, 82.2%; week 4, 90.0%) and nonremission (PPV: week 2, 80.0%; week 4, 90.0%); early nonresponse at week 4 was a statistically significant baseline predictor for 12-week nonresponse; and PANSS-6 had similar predictive significance as PANSS-30. However, outcomes were heterogeneous using CGI-I. Conclusion: In youths with first-episode psychosis showing early nonresponse to aripiprazole or extended-release quetiapine, switching antipsychotic drug should be considered. PANSS-6 is a feasible and clinically relevant alternative to PANSS-30 to predict 12-week nonresponse/nonremission. Clinical trial registration information: Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis; https://www.clinicaltrials.gov/; NCT01119014.