PURPOSE: Long-term blood pressure variability (BPV) has emerged as a risk factor for various health problems, including eye diseases, independent of blood pressure (BP) levels. Yet, its role in age-related macular degeneration (AMD) progression remains unknown. This study aimed to assess associations between long-term BPV and the risk of AMD. DESIGN: Prospective analysis of 14-year data from the ALIENOR (Antioxydants, LIpides Essentiels, Nutrition et maladies OculaiRes) study, a French longitudinal population-based cohort study (2006-2020). PARTICIPANTS: The ALIENOR study included 963 participants aged ≥73 years from the Three-City (3C) study in Bordeaux, for an ophthalmic follow-up. METHODS: Systolic BPV (SBPV), diastolic BPV (DBPV), and pulse pressure variability (PPV) were determined as the standard deviation of available BP measurements in 3C visits (1999-2017). MAIN OUTCOME MEASURES: Age-related macular degeneration was assessed using retinal color photographs and OCT imaging every 2 years from 2006 to 2020. Shared random effects joint models fitted BPV current values and quantified their effect on AMD onset. The implemented Bayesian approach yielded the mean of adjusted posterior hazard ratios of AMD and their 95% credibility intervals (CrIs). RESULTS: Of the 692 (median age: 79.0 years; 63.5% female) and 475 (median age: 78.5 years; 61.1% female) at-risk participants, 10% and 36% developed advanced and intermediate AMD, respectively. The hazard of advanced AMD was significantly increased by 54% for a 5-mmHg increase in DBPV (adjusted hazard ratio [aHR]: 1.54, 95% CrI: 1.02-2.44), whereas statistical significance was not reached for a 5-mmHg increase in SBPV (aHR: 1.20, 95% CrI: 0.96-1.51) and PPV (aHR: 1.17, 95% CrI: 0.88-1.54). Conversely, BPV was not significantly associated with intermediate AMD (aHR: 0.96, 95% CrI: 0.83-1.11; aHR: 0.96, 95% CrI: 0.71-1.30; and aHR: 0.92, 95% CrI: 0.77-1.09; for a 5-mmHg increase in SBPV, DBPV, and PPV, respectively). CONCLUSIONS: This study suggested that long-term variability in BP may be associated with an increased risk of advanced AMD, particularly for DBP. These findings underscore the need for further research to confirm this association, explore the underlying mechanisms, and propose potential interventions that could mitigate this risk. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.