ABSTRACT.- The reasons for culling dairy cows in Uruguay are largely unknown. This study aimed to describe the culling rates of dairy cows and identify the causes of cow culling in 12 commercial herds in Uruguay. We conducted a prospective longitudinal observational study from June 2019 to May 2020 on 12 dairy farms stratified by herd size. Six farms with 51-199 cows, five with 200-500 cows, and one farm with more than 500 cows in the departments of Colonia and San José were included. The cows were pure Holstein and Holstein-Jersey crossbreeds. The overall dairy cow population on these 12 farms was 3126 cows (range: 74-740 cows per farm). The data were analyzed using descriptive statistics. The total annual culling rate was 23.1% (721/3126), including sales to slaughter (18.1%; 565/3126), on-farm mortality (4.5%; 141/3126), and dairy sales (0.5%; 15/3126). Cow culling for slaughter because of health (including reproductive) problems represented 70.7% (510/721) of the overall culling rate, most of which were due to reproductive failure (29.3%, 211/721), mastitis (25.9%, 187/721), poor udder conformation (6.2%, 45/721), lameness (4.6%, 33/721), and other diseases (4.7%, 34/721). Mortality represented 19.6% (141/721) of the overall culling rate. Cow culling for slaughter due to health (including reproductive) problems and mortality constituted 90.3% (651/721) of the total culled cows. In conclusion, dairy cows were culled mainly due to illnesses that lead to slaughter or death. Implementing effective measures to improve reproductive rates, reduce mastitis and lameness, and prevent other diseases, such as leukosis, paratuberculosis, and digestive disorders in the studied population would reduce cow culling, increasing cow longevity, animal welfare, and farm profitability. © 2025 by the authors. Licensee MDPI, Basel, Switzerland.