Mekong Delta of Vietnam is the prominent area of the striped catfish (Pangasianodon hypophthalmus) production and remains the top exporters in the world. However, diseases have been one of the significant problems for the profitability of striped catfish farming in the area stated. An investigation on diseases was carried out in the major striped catfish culture areas in An Giang province and Can Tho city during the year 2019. Forty different cases 23 from An Giang and 17 from Can Tho were collected from the study area. 17 other cases, 4 from An Giang and 13 from Can Tho were also collected as a secondary data from the Can Tho sub-aquaculture department. Clinical diagnosis and the differential diagnosis were performed on the farm and samples were collected to the aquatic pathology lab of College of Aquaculture and Fisheries (CAF), Can Tho University (CTU). Clinical signs, bacteriological, and PCR results were noted and analyzed to generate meaningful information. Trichodina sp., Gyrodactylus sp., Dactylogyrus sp., Epistylis sp. and Myxobolus sp., were the major parasites found in the study area. Hemorrhagic disease caused by A. hydrophila and BNP caused by E. ictaluri, and their co-infection were the major disease and the major causative agent found in the study area. Whitish gill and liver disease were also detected in many cases in which the causative agent is still unknown and suggests further research.