Objective: Low hemoglobin negatively affects health in the elderly, but research about the association with risk for depression is limited. We investigated the association between baseline hemoglobin concentrations and incident depression in a cohort of nondepressed elderly individuals. Methods: As part of the Northern Italian Progetto Veneto Anziani (PRO.V.A.) study, randomly drawn, community-dwelling subjects aged ≥ 65 years underwent prospective clinical and laboratory assessments between October 1995 and December 2002. The association between baseline hemoglobin and depression was assessed with adjusted Cox regression analyses. Baseline serum hemoglobin concentrations were further categorized in gender-specific tertiles; anemia was defined as serum hemoglobin < 13 g/dL for men and < 12 g/dL for women. Moreover, hemoglobin concentration was measured at follow-up, and changes in concentration from baseline to follow-up were investigated. Depression was defined by a score of ≥ 11/30 on the validated Geriatric Depression Scale and confirmed by psychogeriatric specialists. Results: Among 1,303 elderly individuals (566 men, 737 women) without depression at baseline, 294 subjects (177 women, 117 men; global incidence rate = 50 [95% confidence interval (CI), 0-170] per1,000 patient years) developed depression during 4.4 years of follow-up. Low baseline serum hemoglobin concentration was most strongly associated with incident depression at follow-up in men (hazard ratio [HR] = 1.39; 95% CI, 1.12-1.69; P = .002), but not in women (P = .50). Men with the lowest baseline tertile hemoglobin concentration (HR = 1.68; 95% CI, = 1.02-3.08; P = .04) or with anemia (HR = 2.02; 95% CI, = 1.13-3.64; P = .02) had greater risk of depression, whereas findings were nonsignificant for women. Low follow-up hemoglobin concentration in men was less strongly associated with incident depression (HR = 1.15; 95% CI, 1.01-1.33; P = .05), as were the lowest endpoint tertile hemoglobin concentration (P = .03) and presence of anemia (P = .05). © Copyright 2016 Physicians Postgraduate Press, Inc.