Objective: This study aimed to establish whether antipsychotic (AP) use in patients with dementia negatively affects quality of life (QoL) independent of neuropsychiatric symptoms (NPS)., Method: We tested 290 patients with dementia living in nine nursing homes throughout the Netherlands in a longitudinal study. The measurements were repeated every 6 months over 2 years. We studied the change in NPS and AP use and their effect on QoL over time in two separate generalized estimating equations. We assessed QoL and NPS using the Qualidem questionnaire and the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH), respectively., Results: Antipsychotic prescriptions did not significantly change participant QoL, whereas NPI-NH total score changes consistently predicted changes in QoL. According to the Qualidem, the development of QoL in patients who chronically used APs did not differ from AP-free patients, except on the restless tense behavior subscale. AP-free patients' "restless tense behavior" improved compared with patients who chronically used APs, who showed a slight deterioration in these symptoms; however, this effect did not significantly influence total QoL., Conclusion: Antipsychotic use does not necessarily have detrimental effects on the QoL of patients with dementia; rather, NPS consistently and negatively affects QoL. The use of APs to treat NPS is justified when used carefully (i.e., their benefits and side effects should be monitored)., (Copyright © 2012 John Wiley & Sons, Ltd.)