Objective: To verify whether depression, defined as a 15-item Geriatric Depression Scale (GDS) > 6, is associated with greater drug utilization by elderly patients. Population: 2568 patients enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study. Main outcome measure: Polypharmacy, ie, the daily use of at least 3 drugs, excluding antidepressant and anxiolytic agents, in the month prior to admission. Method: Home therapy data were collected according to a validated procedure. Correlates of polypharmacy were assessed by logistic regression analysis in the whole population and in subgroups for which indexes of disease severity were available. Results: GDS > 6 was found to be positively correlated with polypharmacy (odds ratio 1.22; 95% confidence interval 1.01-1.48) as were older age, comorbidity, hypertension, diabetes mellitus, congestive heart failure, and renal failure. Negative correlates of polypharmacy were smoking habit and alcohol consumption, and GDS > 6 was negatively associated with the use of analgesic (11.8% vs 15.6%, p = 0.012). In the subgroups with congestive heart failure and chronic renal failure, GDS > 6 was strictly associated with greater disease severity, but did not correlate with polypharmacy in multivariable models including indexes of disease severity. Conclusions: Depressed mood is associated with polypharmacy in the broad elderly population. However, when indexes of disease severity were considered, the association was lost, indicating that depression is a marker of the burden of disease and does not increase drug consumption per se.