Background: Prolonged grief disorder (PGD) and depression are recognized as distinct emotional-distress disorders for bereaved family caregivers. However, this distinction has been mostly validated in cross-sectional studies, neglecting the dynamic characteristics of bereaved caregivers' emotional distress. Objective: To validate the distinction between symptoms of PGD and depression across the first bereavement year for family caregivers of terminally ill cancer patients. Methods: In this descriptive, longitudinal study of 394 bereaved Taiwanese family caregivers, we measured symptoms of PGD and depression by the Prolonged Grief-13 and Center for Epidemiologic Studies Depression (CES-D) scales at 6 and 13 months postloss, respectively. Agreement between cases of PGD and severe depressive symptoms (CES-D score ≥ 16) was analyzed by Cohen's kappa. Structural distinctiveness was longitudinally examined using confirmatory bifactor modeling. Results: Agreement was poor between cases of PGD and severe depressive symptoms at 6 and 13 months postloss (kappa = .16 [confidence interval = .09, .22] and .12 [confidence interval = .03, .19], respectively). Symptoms of PGD and depression shared a general factor, but were distinct as shown by their significant specific factor loadings at 6 and 13 months postloss. Confirmatory bifactor models showed structural invariance (confirmatory fit index difference < .01 and χ2 difference P > .05) between 6 and 13 months postloss. Conclusion: Symptoms of PGD and depression were confirmed as distinct across the first year of bereavement. Health care professionals should recognize early in bereavement that symptoms of PGD and depression are distinct, identify high-risk groups, and provide care tailored to caregivers' unique needs to facilitate recovery from bereavement-related emotional-distress disorders.