BACKGROUND: Although spiritual care is associated with less aggressive medical care at the end of life (EOL), it remains infrequent. It is unclear if the omission of spiritual care impacts EOL costs. METHODS: A prospective, multi-site study of 339 advanced cancer patients accrued subjects from September 2002 to August 2007 from an outpatient setting and followed them until death. Spiritual care was measured by patients’ reports that the health care team supported their religious/spiritual needs. EOL costs in the last week were compared among patients reporting that their spiritual needs were inadequately supported versus those who reported that their needs were well supported. Analyses were adjusted for confounders (eg, EOL discussions). RESULTS: Patients reporting that their religious/spiritual needs were inadequately supported by clinic staff were less likely to receive a week or more of hospice (54% vs 72.8%; P 1⁄4 .01) and more likely to die in an intensive care unit (ICU) (5.1% vs 1.0%, P 1⁄4 .03). Among minorities and high religious coping patients, those reporting poorly supported religious/spiritual needs received more ICU care (11.3% vs 1.2%, P 1⁄4 .03 and 13.1% vs 1.6%, P 1⁄4 .02, respectively), received less hospice (43.% vs 75.3% 1 week of hospice, P 1⁄4 .01 and 45.3% vs 73.1%, P 1⁄4 .007, respectively), and had increased ICU deaths (11.2% vs 1.2%, P 1⁄4 .03 and 7.7% vs 0.6%, P 1⁄4 .009, respectively). EOL costs were higher when patients reported that their spiritual needs were inadequately supported ($4947 vs $2833, P 1⁄4 .03), particularly among minorities ($6533 vs $2276, P 1⁄4 .02) and high religious copers ($6344 vs $2431, P 1⁄4 .005). CONCLUSIONS: Cancer patients reporting that their spiritual needs are not well supported by the health care team have higher EOL costs, particularly among minorities and high religious coping patients.