OBJECTIVES: To examine the effect of religion and spirituality on social support, psychological functioning, and physical health in medically ill hospitalized older adults. DESIGN: Cross-sectional survey. SETTING: Duke University Medical Center. PARTICIPANTS: A research nurse interviewed 838 consecutively admitted patients aged 50 and older to a general medical service. MEASUREMENTS: Measures of religion included organizational religious activity (ORA), nonorganizational religious activity, intrinsic religiosity (IR), self-rated religiousness, and observer-rated religiousness (ORR). Measures of spirituality were self-rated spirituality, observer-rated spirituality (ORS), and daily spiritual experiences. Social support, depressive symptoms, cognitive status, cooperativeness, and physical health (self-rated and observer-rated) were the dependent variables. Regression models controlled for age, sex, race, and education. RESULTS: Religiousness and spirituality consistently predicted greater social support, fewer depressive symptoms, better cognitive function, and greater cooperativeness (P<.01 to P<.0001). Relationships with physical health were weaker, although similar in direction. ORA predicted better physical functioning and observer-rated health and less-severe illness. IR tended to be associated with better physical functioning, and ORR and ORS with less-severe illness and less medical comorbidity (all P<.05). Patients categorizing themselves as neither spiritual nor religious tended to have worse self-rated and observer-rated health and greater medical comorbidity. In contrast, religious television or radio was associated with worse physical functioning and greater medical comorbidity. CONCLUSION: Religious activities, attitudes, and spiritual experiences are prevalent in older hospitalized patients and are associated with greater social support, better psychological health, and to some extent, better physical health. Awareness of these relationships may improve health care.