Objective: Research is needed to determine specific factors that contribute to the success of nonpharmacologic interventions. In this study, we examined the influence of personal characteristics (demographic, medical, and functional variables) and possible barriers (eg, staff or family barriers) on the efficacy of nonpharmacological interventions in reducing agitation. Method: Agitation was systematically observed at baseline and intervention stages using the Agitation Behavior Mapping Instrument (ABMI) in a sample of 89 residents from 6 Maryland nursing homes (mean age = 85.9 years). Each participant received interventions based on an individualized algorithm (TREA-Treatment Routes for Exploring Agitation), which identifies unmet needs and matches interventions to needs and to the participant's sensory, cognitive, and functional abilities, as well as to self-identity and preferences. The study was conducted between June 2006 and December 2011. Results: Analyses revealed that decreased levels of agitation during intervention correlated significantly with higher levels of cognitive function (r = 0.36, P < .001), with fewer difficulties in the performance of activities of daily living (r = 0.29, P < .01), speech (r = 0.47, P < .001), communication (r = 0.23, P < .05), and responsiveness (r = 0.28, P < .01). In addition, less reduction of agitation during intervention was significantly related to the presence of staff barriers (eg, refusals, interruptions) (r = -0.38, P < .001) and the occurrence of pain (r = -0.21, P ≤ .05). Conclusions: The findings elucidate the characteristics of those who are most likely to respond to TREA intervention, and point to the need of systemic changes to reduce staff-related barriers and to improve methodologies for increasing the impact of intervention on those at the lowest levels of functioning.