Introduction: Arsenic-based pesticides, the only chemical solution used in viticulture until 2001 to control esca, are classified as definite carcinogens. Estimates of the number of people exposed and calculations of exposure prevalence among agricultural workers have never been conducted. Methods: Agricultural workers were identified using agricultural censuses (1979/1988/2000). A distinction was made between workers on professional vineyards (the sole users of arsenic) and those cultivating vines for recreational purposes. Exposure was assessed using a crop-specific exposure matrix (Matphyto-Arsenic). Exposure indicators were calculated in accordance with the years of the agricultural censuses. The number of exposed workers was calculated using the probabilities of Matphyto-Arsenic use and the workforce numbers of professional vineyards. Exposure prevalence rates were calculated by comparing these exposed workers with the workforce of other agricultural workers. Results: Between 1979 and 2000, the number of exposed workers decreased by nearly 40%—from 101,359 to 61,376—in parallel with a decline of more than 50% in the workforce of wine-growing operations. The prevalence of exposure among family labor on all agricultural holdings in metropolitan France remained stable (3.6% to 4.2%) over the study period. It increased among family labor and salaried workers on farms growing grapes for recreational or professional purposes (10.5% to 19.6%) and on those growing grapes exclusively for professional purposes (20% to 25%). Discussion: This study is the first to document the prevalence of exposure and the number of winegrowers exposed to arsenic compounds. Although banned since 2001, it seems important—given their proven carcinogenic effects, their latency, and the significant number of exposed individuals—to raise awareness among physicians (occupational and general practitioners) as well as workers to ensure better post-occupational monitoring and, where appropriate, recognition as an occupational disease.