The objective of this study was to determine if the orally disintegrating tablet formulation of olanzapine, Zvprexa(R) Zydis(R), would facilitate antipsychotic medication compliance in acutely ill, non-compliant patients. Eighty-five acutely ill patients with schizophrenia or schizoaffective disorder who met medication non-compliance criteria received open-label olanzapine orally disintegrating tablets (10-20 mg/d) for up to 6 wk. Improvement in medication compliance was assessed using various rating scales to measure changes in psychopathology, medication-taking and compliance attitudes, and nursing care burden. Safety, variables were also measured. Significant improvement from baseline was demonstrated in the positive and Negative Syndrome Scale total score at Week 1 and subsequently (p < 0.001). Significant improvement from baseline was also seen in various scales measuring medication compliance, attitude, and nursing care burden (p < 0.05). Olanzapine orally disintegrating tablets were well-tolerated. Olanzapine orally disintegrating tablets may benefit acutely ill, non-compliant schizophrenic patients by facilitating acceptance of active antipsychotic drug therapy.