This study investigated the effects of dietary supplementation with hyperimmunized egg yolk powder (HEYP) on diarrhoea incidence and intestinal health of weaned pigs. Two kinds of HEYP were used, one is multivalent HEYP against mixed Escherichia coli (E. coli) (K88-K99-987P) antigens and the other is the mixture of three monovalent HEYP against single E. coli K88, K99 or 987P antigen, respectively. A total of 180 weaned pigs were assigned to 5 dietary treatments: control diet (CON), 3 or 30 g/kg of two kinds of HEYP diets. Pigs fed HEYP diets had a lower diarrhoea incidence, lower E. coli numbers in faeces and ameliorated mucosal morphology in the duodenum, accompanied by a tendency to reduce inflammation response and intestinal permeability compared with CON. There were no significant differences in the dosage effects of either HEYP. Therefore, anti-(K88-K99-987P) HEYP might be an effective feed additive to protect weaned pigs against enterotoxigenic E. coli.