BACKGROUND: Age-related macular degeneration (AMD) is a growing public health concern worldwide, as one of the leading causes of vision impairment. We aimed to estimate global, national, and region-specific prevalence and disability-adjusted life-years (DALYs) along with tobacco as a modifiable risk factor to aid public policy addressing AMD. METHODS: Data on AMD were extracted from the Global Burden of Disease, Injuries, and Risk Factor Study 2021 database in 204 countries and territories, 1990-2021. Vision impairment was defined and categorised by severity as follows: moderate to severe vision loss (visual acuity from <6/18 to 3/60) and blindness (visual acuity <3/60 or a visual field <10 degrees around central fixation). The burden of vision impairment attributable to AMD was subsequently estimated. These estimates were further stratified by geographical region, age, year, sex, Healthcare Access and Quality (HAQ) Index, and Socio-demographic Index (SDI) levels. Additionally, the effect of tobacco use, a modifiable risk factor, on the burden of AMD was analysed, and projections of AMD burden were estimated through to 2050. These projections also included scenario modelling to assess the potential effects of tobacco elimination. FINDINGS: Globally, the number of individuals with vision impairment due to AMD more than doubled, rising from 3·64 million (95% uncertainty inverval [UI] 3·04-4·35) in 1990 to 8·06 million (6·71-9·82) in 2021. Similarly, DALYs increased by 91% over the same period, from 0·30 million (95% UI 0·21-0·42) to 0·58 million (0·40-0·80). By contrast, age-standardised prevalence and DALY rates declined, with prevalence rates decreasing by 5·53% (99·50 per 100 000 of the population [95% UI 83·16-118·04] in 1990 to 94·00 [78·32-114·42] in 2021) and DALY rates dropping by 19·09% (8·38 [5·70-11·53] to 6·78 [4·70-9·32]). These rates showed a consistent decrease in higher SDI quintiles, reflecting the negative correlation between HAQ Index and AMD burden. A general downward trend was observed from 1990 to 2021, with the largest age-standardised reduction occurring in the low-middle SDI quintile. The global contribution of tobacco to age-standardised DALYs decreased by 20%, declining from 12·45% (95% UI 7·73-17·37) in 1990 to 9·96% (6·12-14·06) in 2021. By 2050, the number of individuals affected by AMD is projected to increase from 3·40 million males (95% UI 2·81-4·17) in 2021 to 9·02 million (5·72-14·20) and from 4·66 million females (3·88-5·65) to 12·32 million (8·88-17·08). Eliminating tobacco use could reduce these numbers to 8·17 million males (5·59-11·92) and 11·15 million females (8·58-14·48) in 2050. INTERPRETATION: While the total prevalence and DALYs due to AMD have steadily increased from 1990 to 2021, age-standardised prevalence and DALY rates have declined, probably reflecting the effect of population ageing and growth. The consistent decrease in age-standardised rates with higher SDI levels highlights the crucial role of health-care resources and public policies in mitigating AMD-related vision impairment. The downward trend observed from 1990 to 2021 might also be partially attributed to the reduced effect of tobacco as a modifiable risk factor, with declines in tobacco use seen globally and across all SDI quintiles. The burden of vision impairment due to AMD is projected to increase to about 21·34 million in 2050. However, effective tobacco regulation has the potential to substantially reduce AMD-related vision impairment, particularly in lower SDI quintiles where health-care resources are limited. FUNDING: Gates Foundation.