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Patients consider their human connection with a physician an important aspect of end-of-life (EOL) care. In this study, the authors sought to develop and validate a measure of therapeutic alliance between patients with advanced cancer and their physicians and to evaluate the effects of therapeutic alliance on EOL experiences and care.The Human Connection (THC) scale was developed to measure the extent to which patients felt a sense of mutual understanding, caring, and trust with their physicians. The scale was administered to 217 patients with advanced cancer along with measures of attributes that have been related hypothetically to therapeutic alliance, including emotional acceptance of terminal illness. EOL outcomes in 90 patients who died during the study also were examined.The 16-item THC questionnaire was consistent internally (Cronbach α = .90) and valid based on its expected positive association with emotional acceptance of terminal illness (r = .31; P < .0001). THC scores were related inversely to symptom burden (r = −.19; P = .006), functional status (Karnofsky performance status; r = .22; P = .001), and mental illness (THC score: 50.69 for patients with any Diagnostic and Statistical Manual [DSM] diagnosis vs 55.22 for patients with no DSM diagnosis; P = .03). THC scores were not associated significantly with EOL discussions (P = .68). Among the patients who died, EOL intensive care unit (ICU) care was associated inversely with therapeutic alliance (THC score: 46.5 for patients who received ICU care vs 55.5 for patients without ICU care; P = .002), so that patients with higher THC scores were less likely to spend time in the ICU during the last week of life.The THC scale is a valid and reliable measure of therapeutic alliance between patients with advanced cancer and their physicians. In addition, there was no evidence to suggest that EOL discussions harm patients' therapeutic alliance. A strong therapeutic alliance was associated with emotional acceptance of a terminal illness and with decreased ICU care at the EOL among patients with advanced cancer. Cancer 2009. © 2009 American Cancer Society.