Agitation in nursing home residents presents a serious challenge to caregivers and may place residents at risk for harm. Understanding the etiology of agitation can assist clinicians in developing nonpharmacologic interventions for preventing and treating this problem. The purpose of this study was to examine independent and common predictors of resident agitation with structural equation modeling. Agitation was measured with both a standardized staff report rating scale and direct behavioral observation. No indirect or mediating effects were found. Cognitive impairment, vision and hearing impairment, and gender were found to be independent predictors of agitation as measured by direct behavioral observation. Only cognitive impairment was found to be predictive of agitation as measured by the standardized staff report scale. An unexpected finding was that vision impairment appeared to exert a protective effect for agitation in these severely cognitively impaired residents. The clinical implications of these findings are discussed as well as the relative merits of the two methods of measuring agitation.