Abstract: Epidemiological investigation of swine diseases with clinical significance in the border area of Shandong, Hebei and Henan Provinces is of great importance to reduce the occurrence of major swine diseases in this region. In this study, a total of1 196 porcine samples were recovered from the border area of Shandong, Hebei and Henan Provinces from March 2016 to October 2017, and the antibody and antigen of classical swine fever virus（CSFV）, porcine reproductive and respiratory syndrome virus（PRRSV）, porcine pseudorabies virus（PRV）, and porcine epidemic diarrhea virus（PEDV） were detected by commercially available ELISA kits. The results showed that the antibody and antigen positive rate of CSFV was 82.94%（496/598） and 2.56%（6/234）, respectively; the antibody positive rate of PRRSV was 81.94%（490/598）, and the antigen positive rate of the clinical samples from the swine with reproductive disorders was 20.73%（51/246）; the g B and g E antibody positive rate of PRV was72.78%（484/665） and 14.59%（97/665）, respectively; the overall antibody positive rate of PEDV was 47.50%（95/200）, among which the immunized and un-immunized population was 63.30% and 35.00%, respectively. Our investigation demonstrated that the epidemic status of swine diseases with clinical significance in this region is severe, and the vaccinations against the related epidemic diseases should be further strengthened.