We sought to test whether variations across regions in end-of-life (EOL) treatment intensity are associated with regional differences in patient preferences for EOL care. Dual-language (English/Spanish) survey conducted March to October 2005, either by mail or computer-assisted telephone questionnaire, among a probability sample of 3480 Medicare part A and/or B eligible beneficiaries in the 20% denominator file, age 65 or older on July 1, 2003. Data collected included demographics, health status, and general preferences for medical care in the event the respondent had a serious illness and less than 1 year to live. EOL concerns and preferences were regressed on hospital referral region EOL spending, a validated measure of treatment intensity. A total of 2515 Medicare beneficiaries completed the survey (65% response rate). In analyses adjusted for age, sex, race/ethnicity, education, financial strain, and health status, there were no differences by spending in concern about getting too little treatment (39.6% in lowest spending quintile, Q1; 41.2% in highest, Q5; P value for trend, 0.637) or too much treatment (44.2% Q1, 45.1% Q5; P = 0.797) at the end of life, preference for spending their last days in a hospital (8.4% Q1, 8.5% Q5; P = 0.965), for potentially life-prolonging drugs that made them feel worse all the time (14.4% Q1, 16.5% Q5; P = 0.326), for palliative drugs, even if they might be life-shortening (77.7% Q1, 73.4% Q5; P = 0.138), for mechanical ventilation if it would extend their life by 1 month (21% Q1, 21.4% Q5; P = 0.870) or by 1 week (12.1% Q1, 11.7%; P = 0.875). Medicare beneficiaries generally prefer treatment focused on palliation rather than life-extension. Differences in preferences are unlikely to explain regional variations in EOL spending.