CONTEXT: Cognitive impairment commonly affects cancer patients. OBJECTIVES: To examine whether minor cognitive impairment in patients with advanced cancer is associated with the intensity of end-of-life (EOL) care or modifies the influence of patient and caregiver preferences on the intensity of EOL care. METHODS: Data were derived from structured interviews with 221 advanced cancer patient-caregiver dyads in the Coping with Cancer Study, a multisite, longitudinal cohort study. Deficits in patients' cognitive function were identified using the Short Portable Mental Status Questionnaire (SPMSQ). Patients and caregivers reported preferences regarding life-extending vs. symptom-directed care. Information regarding EOL care was obtained from postmortem interviews with caregivers. Logistic regression analyses modeled main and interactive effects of patients' cognitive impairment and patients' and caregivers' treatment preferences on intensive EOL care. RESULTS: Cognitive impairment was associated with less intensive EOL care (odds ratio [OR] = 0.56; 95% confidence interval [CI]: 0.34-0.91). Patients and caregivers had poor agreement regarding preferences for life-extending vs. symptom-directed care (Φ = 0.10; χ(2)=2.32, df = 1, P = 0.13). Patient preference for life-extending care predicted intensive EOL care irrespective of cognitive status (adjusted odds ratio [AOR] = 2.11; 95% CI: 1.04-4.28). For patients with no errors on the SPMSQ, caregiver preference for life-extending care was unrelated to intensive EOL care (AOR = 0.40; 95% CI: 0.09-1.77). However, the association between caregiver preference for life-extending care and intensive EOL care increased by nearly a factor of seven for every error on the SPMSQ (interaction AOR = 6.90; 95% CI: 1.40-34.12). CONCLUSION: Cognitive impairment in patients with advanced cancer is associated with less intensive EOL care. Caregivers' influence on intensive EOL care dramatically increases with minor declines in patients' cognitive function.