BackgroundDepression has been cross-sectionally associated with short telomeres as a measure of biological age. However, the direction and nature of the association is currently unclear.AimsWe examined whether short telomere length is associated with depression cross-sectionally as well as prospectively and genetically.MethodTelomere length and three polymorphisms, TERT, TERC and OBFC1, were measured in 67306 individuals aged 20–100 years from the Danish general population and associated with register-based attendance at hospital for depression and purchase of antidepressant medication.ResultsAttendance at hospital for depression was associated with short telomere length cross-sectionally, but not prospectively. Further, purchase of antidepressant medication was not associated with short telomere length cross-sectionally or prospectively. Mean follow-up was 7.6 years (range 0.0–21.5). The genetic analyses suggested that telomere length was not causally associated with attendance at hospital for depression or with purchase of antidepressant medication.ConclusionsShort telomeres were not associated with depression in prospective or in causal, genetic analyses.