OBJECTIVE: The objective of this analysis was to explore the association of improvement in QoL and depressive symptoms with robust acute treatment response of olanzapine (OLZ) versus haloperidol (HAL). METHODS: Data was analyzed post-hoc from a double-blind, randomized (OLZ versus HAL), trial of 1996 patients with schizophrenia or a related disorder. The treatment response was classified into four groups based on improvement of the Brief Psychiatric Rating Scale (BPRS) total scores at 6 weeks: < 20%, 20-40%, 40-65% and >65% improvement. Mean percent changes of Quality of Life Scale (QLS) scores and Montgomery-Asberg Depression Rating Scale (MADRS) were determined. RESULTS: There was a significant positive association between the more robust level of response (i.e., >65%) and improvements in depressive symptoms and QLS across treatment groups. Patients treated with OLZ started to access moderate improvement (>10% improvement) in QLS once they attained a 20% or greater improvement in BPRS while for the HAL-treated patients, only those who had a 65% or greater response in BPRS could exceed moderate QLS improvement. The mean percent change in QLS in the 20-40% BPRS response group was 13.4% for OLZ versus 1% for HAL (p = 0.031) and in the 65% or greater BPRS response group was 41.8% for OLZ versus 32.8% for HAL (p = 0.45). Similar observations were demonstrated in improvement on the MADRS. For patients with a 40-65% BPRS response, the improvement in MADRS was 34.9% for OLZ versus 6.7% for HAL (p=0.027). CONCLUSION: A more robust categorical acute treatment response resulted in greater improvement in QoL and depressive symptoms across treatment groups. For patients attaining the same level of acute treatment response though, there may be significantly greater improvements in QoL and depressive symptoms enjoyed by OLZ-treated patients compared to those treated with HAL.