Objective: Depression among older adults predicts mortality after acute hospitalization. Depression is highly heterogeneous in its presentation of symptoms, whereas individual symptoms may differ in predictive value. This study aimed to investigate the prevalence of individual cognitive-affective depressive symptoms during acute hospitalization and investigate the predictive value of both overall and individual cognitive-affective depressive symptoms for mortality between admission up to 3-month postdischarge among older patients. Methods: A prospective multicenter cohort study enrolled 401 acutely hospitalized patients 70 years and older (Hospitalization-Associated Disability and impact on daily Life Study). The predictive value of depressive symptoms, assessed using the Geriatric Depression Scale 15, during acute hospitalization on mortality was analyzed with multiple logistic regression. Results: The analytic sample included 398 patients (M (SD) = 79.6 (6.6) years; 51% men). Results showed that 9.3% of participants died within 3 months, with symptoms of apathy being most frequently reported. The depression total score during hospitalization was associated with increased mortality risk (admission: odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.2-1.3; discharge: OR = 1.2, 95% CI = 1.2-1.4). Stepwise multiple logistic regression analyses yielded the finding that feelings of hopelessness during acute hospitalization were a strong unique predictor of mortality (admission: OR = 3.6, 95% CI = 1.8-7.4; discharge: OR = 5.7, 95% CI = 2.5-13.1). These associations were robust to adjustment for demographic factors, somatic symptoms, and medical comorbidities. Conclusions: Symptoms of apathy were most frequently reported in response to acute hospitalization. However, feelings of hopelessness about their situation were the strongest cognitive-affective predictor of mortality. These results imply that this item is important in identifying patients who are in the last phase of their lives and for whom palliative care may be important.