We investigated the effects of monensin controlled-release capsule (CRC; Kexxtone, Eli Lilly and Company Ltd., Indianapolis, IN) preventative ketosis treatment on the traditional cheesemaking process as well as the final characteristics of Parmigiano Reggiano (PR) cheese. The use of this prevention product to reduce the incidence of ketosis in transition dairy cows was approved by the European Medicines Agency in 2013. No previous studies are available concerning the effects of this treatment on prolonged-ripening cheese production such as PR. In PR cheese production, feed, feed additives, and cow treatments are strictly regulated to avoid any possible interference with traditional manufacturing processes. For these reasons, on 1 farm where all milk was used for PR cheese production, monensin CRC was administered to 33 cows, 21 d before calving in the monensin-treated group (TRT), whereas untreated cows with similar breed and parity characteristics constituted the control group (CTR). For 20 wk, milk obtained from each group and whey starter were separately managed and transported in the cheese factory, where 2 cheese wheels per group were produced daily, making 552 PR cheese wheels in total. Morning bulk tank milk composition, cheesemaking properties, and whey starter fermentation activities were analyzed twice a week. Every aspect of the cheesemaking process was recorded and the resulting cheese was evaluated after 36 h and 6, 12, and 18 mo from production for yield, texture defects, composition, and fatty acids profile. Milk from the 2 groups differed for somatic cell content (TRT = 3.04 vs. CTR = 4.06, somatic cell score), total bacterial count (TRT = 4.08 vs. CTR = 6.08 × 1,000 cfu/mL), titratable acidity (TRT = 3.66 vs. CTR = 3.72 Soxhlet-Henkel degrees/50 mL), and casein content percentage (TRT = 2.4 vs. CTR = 2.5%). Whey starter parameters were comparable between the 2 groups. Final cheese composition and organoleptic profile were not influenced by the treatment, except for C18:1 content being enhanced (TRT = 22.8 vs. CTR = 20.8% of fatty acids). Percentage of defected ripened cheese was significantly lower in the treated group, both at x-ray evaluation performed at 6 mo (TRT = 6.2 vs. CTR = 12.3%) and at the consortium inspection, performed at 12 mo of ripening (TRT = 1.5 vs. CTR = 6.5%). On the other hand, average cheese yield at 18 mo of ripening was partially reduced (TRT = 7.5 vs. CTR = 7.7%). Overall, the use of monensin CRC had no negative effect on the cheesemaking process, prolonged ripening cheese characteristics, milk composition, or whey starter quality.