A cross sectional study was conducted from November 2020 to March 2021 on calves and human Cryptosporidiosis in Libo Kemkem district, North West Ethiopia. The objective of the study was determining the prevalence and associated risk factors of Cryptosporidiosis in calves and hospitalized human. A total of 193 calves with age group ranging from one week up to 12 months from three different agro ecologically kebeles and 122 stool samples from humans admitted at the district hospital were used for this study. The three kebeles were selected purposively and individual calves were selected using simple random method and allocated proportionally. For human sample systematic random sampling was used. To identify Cryptosporidium Oocyst; fecal and stool samples were examined using Modified Ziehl–Neelsen staining method. All data were analysed using statistical package for social science Version 20.0 software program and significant level was determined at 95% confidence interval. The over all prevalence of calves and human Cryptosporidium Oocyst found in the study were 15.5% and 11.5% , respectively. A total 9 potential risk factors were investigated for the association with calf Cryptosporidiosis using logistic regression. Age of calf < 6 months (P= 0.021), breed (P= 0.049), body condition (P= 0.043), water source (P= 0.027), fecal consistency (P= 0.016) and hygienic condition (P= 0.042) were found significantly associated by multivariable logistic regression. Similarly, a total of 6 potential risk factors investigated for their association with human Cryptosporidiosis using logistic regression. Source of potable water (P=0.024), immunocompromization (P= 0.007) and contact with domestic animals (P=0.033) were found significantly (P< 0.05) associated with the risk of human Cryptosporidiosis by multivariate logistic regression. The prevalence of Cryptosporidium in calves and human in Libo Kemkem district is so high. Therefore a due attention on zoonotic disease management is mandatory. Key words: - Calf, Cryptosporidium, Hospitalized Human, Libo Kemkem district, Oocyst, prevalence, Risk factors.