Vaccination is essential for disease prevention in swine production; however, repeated intramuscular (IM) injections can compromise animal welfare. This st

Neonatal diarrhea causes significant economic losses in swine production by reducing average daily weight gain (ADWG) and increasing piglet mortality, with Clostridioides difficile (CD) and Clostridium perfringens type A (CPA) being the most common causes. The aim of this study was to evaluate the efficacy of a new commercial vaccine against these agents to minimize diarrhea, pre-weaning mortality, and its negative consequences on weight performance in suckling piglets under field conditions. The study consisted of two randomized, double-blind, negative-controlled field trials (Study A and B) focusing on clinically healthy pregnant sows from commercial pig farms experiencing recurrent neonatal diarrhea. In the meta-analysis of both farms, the control group showed lower performance compared to the vaccine group (least squares means differences) for ADWG (−14.5 g/day, p < 0.001), body weight (−0.33 kg, p < 0.001), and underweight piglets at weaning (6.94%, p = 0.011). The number of piglets with diarrhea (9.76%, p < 0.001) and the percentage of piglets treated with antibiotics for diarrhea (6.09%, p = 0.016) were lower in vaccinated animals compared to controls. No significant differences in pre-weaning mortality were observed. The results of this study suggest that the new commercial vaccine against CD and CPA reduces the incidence of neonatal diarrhea and the associated use of antibiotics, while positively impacts the growth performance of suckling piglets.