Edema disease (ED) is a common fatal disease in newly weaned piglets. To develop an effective control program for ED, we carried out a study to better understand the incidence and spread of the disease and the characteristics of the causative agent. In our study, 69 Escherichia coli strains, isolated from 92 piglets showing clinical signs of ED from 13 provinces in northern Vietnam, were positive for both the VT2e toxin and the F18 major fimbrial subunit gene fedA. Of these, 40 strains (58%) were positive for AIDA and 16 isolates carried one or more enterotoxins. Forty-six (67%) of the 69 VT2e(+)/F18(+) E. coli isolates belonged to classical serotypes (O139:K82, O141: K85, O138:K81, and O149:K91) while the remaining strains did not belong to the common serotypes in pig. Seropathotype 0139:K82(+)/VT2e(+)/F18(+)/AIDA(+) (21 isolates) was the most frequently detected ED-causing E. coli strain. High prevalence of resistance was observed to the common drugs of tetracycline, streptomycin, trimethoprim/sulfamethoxazole, amoxicillin/clavulanic acid, and spectinomycin. Multiple resistances were widely distributed with 84% of isolates resistant to five antibiotics. Sequence analysis demonstrated that the VT2e toxin is identical among E. coli strains causing ED in pig.