BACKGROUND Trajectory studies highlight heterogeneity in treatment response, although they are yet to systematically differentiate between antipsychotic medications. OBJECTIVE To compare treatment response trajectories across antipsychotic medication groups. METHODS Data were analyzed from Phase 1 of CATIE, an 18-month double-blind randomized controlled trial of chronic schizophrenia. Change on recurrent Positive and Negative Syndrome Scale (PANSS) administrations for 1124 patients was used to index treatment response trajectories up to 18 months. Trajectory groups were identified with mixed-mode latent class regression modeling. Groups were derived for all participants, and separately for completers, dropouts, and each antipsychotic medication (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone) and then characterized. RESULTS Trajectory analysis of the entire sample identified that 18.9% of participants belonged to a group of responders. This figure increased to 31.5% for completers, and fell to 14.5% for dropouts. Olanzapine treated patients were significantly more likely than other treatment groups to belong to the trajectory of responders (n=69, 32.55%; Chi=20.13, df=2, p<.01). Separate trajectory analyses of each medication group showed that all medication groups showed two trajectories except olanzapine that had three trajectories and the only trajectory that attained a 20% PANSS reduction by endpoint. CONCLUSIONS Trajectories of treatment response differ between antipsychotic medications and demonstrate substantial heterogeneity in chronic schizophrenia.