Zoonotic Cryptosporidium is chief cause of diarrhea in both developing and developed countries, causing millions of deaths each year. This study was designed to estimate the zoonotic potential of Cryptosporidium in three districts of Khyber Pakhtunkhwa (KPK), i.e. Bannu, Lakki Marwat and Kohat. For this purpose 360 stool samples were collected from the District Headquarter Hospitals of all the three districts and were screened through microscopy. Results yielded an overall prevalence of 11.11%, with significant difference (P<0.05) among different study areas. Prevalence was highest in district Bannu (11.66%), followed by district Lakki Marwat and Kohat with 10% in each district. Statistical analysis revealed significant difference (P<0.05) among children of different age groups with highest disease prevalence in children of less than 5 years of age (21.40%) and lowest in children of 11-15 years of age (15.99%). Cryptosporidium was significantly higher (P<0.05) in study subjects having livestock animal contact and persistent diarrhea, highlighting its zoonotic potential from livestock animals to human beings in the study area. This is first study addressing the one of the main cause of neonatal mortality in Southern KPK and its zoonotic potential.