Retrospective assessment of agricultural workers’ exposure to pesticides is essential for understanding and establishing links between their occupational activities throughout their careers and potential serious health conditions such as cancer or neurodegenerative diseases. There are few reliable tools supported by a precise and structured methodology. Inorganic arsenic is classified as a known human carcinogen by the IARC (International Agency for Research on Cancer) and at the European Union level; the main inorganic arsenic compounds used in agriculture are lead arsenate, calcium arsenate, and sodium arsenite. They act as fungicides and insecticides. Sodium arsenite has been particularly used on grapevines in treatments against wood diseases. By constructing a vineyard-arsenic pesticide exposure matrix (EM), we assessed the use of arsenic compounds in viticulture in mainland France and determined their prevalence of use from 1945 to 2001, the date of their ban. This prevalence of use allowed us to estimate the prevalence of exposure to arsenic-based pesticides, which ranges from 20% to 35% in viticulture for individuals working on professional vineyards. Cross-referencing this MCE with the agricultural censuses (RA) from 1979, 1988, and 2000 provides the number of vineyard workers exposed to arsenic-based pesticides for each census year, as well as a description (age, sex, working hours, etc.) of this population. Our work allows us to estimate that, over the periods considered, between 60,000 and 100,000 people worked on farms using arsenic-based pesticides for vine treatment. These individuals worked on vineyards that, according to the vineyard-arsenic pesticide MCE, used nearly 15 kg of arsenic in 1979, 18.4 kg in 1988, and 26.8 kg in 2000. These figures represent average amounts of arsenic used per farm, and it is important to note that the increase in these amounts is not due to an increase in the dose per hectare but to an increase in the average vineyard area per farm: 4.2 ha in 1979, 5.3 ha in 1988, and 7.6 ha in 2000. To our knowledge, this is the first study to provide prevalence data on exposure to arsenic-based pesticides and a description of the exposed populations, derived from the cross-referencing of a nationwide population-based cohort study with data from the RA. Such data enable the implementation of secondary and tertiary prevention targeted at the identified population, particularly to prevent the development or progression of certain cancers induced by arsenic derivatives and to intervene at the earliest possible stage.