BackgroundOmphalitis is the third most common cause for diseases and infections in newborn calves. Its risk factors are well described in dairy production, but data in beef production is limited. ObjectiveTo identify and quantify the risk factors of omphalitis in cow-calf operations with seasonal indoor calving period. AnimalsNine hundred sixty-four calves included from 22 cow–calf operations in central France were included. MethodsA prospective cohort study involved data collection during two visits for each calf. Simple and multivariable logistic regression analyses evaluated the association between omphalitis and the variables. ResultsAmong 964 included calves, 311 (32.3%) calves had an omphalitis. Accounting for farms’ random effect, risk factors for omphalitis highlighted by the univariable analysis were: absence of navel disinfection (odds ratio (OR) = 2.3, [1.45–3.04]), wetness of bedding calving area (OR = 1.8–2.1, [0.78–2.83]-[0.63–3.57]), cleanliness of calves’ pen (OR =1.6–2.8, [1.22–2.27]-[2.02–3.84]), wetness of calves’ pen bedding (OR = 1.7–3.2, [1.12–2.06]-[3.08–3.84]), calf weight at birth >50 kg (OR = 2.0–5.0, [1.02–2.38]-[1.51–11.1]), umbilical cord length <3 cm (OR = 2.2–2.3, [1.53–3.11]-[1.24–4.38]), and sex (male vs female) (OR = 2.6, [2.08–3.69]). The multivariable analysis, accounting for farms’ random effect, showed that the absence of navel disinfection (OR= 2.2, [1.44–3.09]), wetness of bedding calving area (OR = 1.9–2.4, [0.55–2.83]-[0.59–3.28]), calf weight at birth >50 kg (OR = 1.9–2.6, [1.03–2.56]-[1.43–12.5]) and sex (male vs female) (OR =2.4, [2.09–3.49]) were risk factors for omphalitis. Conclusions and clinical importanceThese observations may help identify animals at early risk (>50 kg, male, short umbilical cord) and pay particular attention to the wetness of bedding and cleanliness of housing. This study highlights the importance of calving-pen bedding, calf characteristics and navel disinfection.