Loneliness is experienced by a third of older adults in the UK and is a modifiable potential risk factor for depressive symptoms. It is unclear how the association between loneliness and depressive symptoms persists over time, and whether it is independent of related social constructs and genetic confounders. We aimed to investigate the association between loneliness and depressive symptoms, assessed on multiple occasions during 12 years of follow-up, in a large, nationally representative cohort of adults aged 50 years and older in England.We did a longitudinal study using seven waves of data that were collected once every 2 years between 2004 and 2017, from adults aged 50 years and older in the English Longitudinal Study of Ageing (ELSA). The exposure was loneliness at baseline (wave two), measured with the short 1980 revision of the University of California, Los Angeles Loneliness Scale (R-UCLA). The primary outcome was a score indicating severity of depression measured at six subsequent timepoints (waves three to eight), using the eight-item version of the Centre for Epidemiologic Studies Depression Scale (CES-D). Analyses were linear multilevel regressions, before and after adjusting for social isolation, social support, polygenic risk scores, and other sociodemographic and health-related confounders. The secondary outcome was depression diagnosis, measured using a binary version of the CES-D.4211 (46%) of 9171 eligible participants had complete data on exposure, outcome, and confounders, and were included in our complete case sample. After all adjustments, a 1-point increase in loneliness score was associated with a 0·16 (95% CI 0·13-0·19) increase in depressive symptom severity score (averaged across all follow-ups). We estimated a population attributable fraction for depression associated with loneliness of 18% (95% CI 12-24) at 1 year of follow-up and 11% (3-19) at the final follow-up (wave eight), suggesting that 11-18% of cases of depression could potentially be prevented if loneliness were eliminated. Associations between loneliness and depressive symptoms remained after 12 years of follow-up, although effect sizes were smaller with longer follow-up.Irrespective of other social experiences, higher loneliness scores at baseline were associated with higher depression symptom severity scores during 12 years of follow-up among adults aged 50 years and older. Interventions that reduce loneliness could prevent or reduce depression in older adults, which presents a growing public health problem worldwide.National Institute on Aging and a consortium of UK Government departments coordinated by the National Institute for Health Research.