This study describes the prevalence of common diseases and pathogens of Pangasianodon hypophthalmus in nursing farms in the Mekong delta, Vietnam, and identifies the preventive husbandry measures in use by these farms and their association with diseases. In a first study, farmers of 63 randomly selected nursing farms in An Giang, Can Tho, and Dong Thap provinces were interviewed using semi-structured questionnaires. Questions included topics on disease occurrence and application of husbandry measures in their last crop. The results showed that prevalence of bacillary necrosis of pangasius (BNP) was 75%, motile Aeromonas septicemia (MAS) 60%, parasitic disease 48%, saprolegniasis 19%, pale gill and liver syndrome 17%, tail rot 14%, and swollen swim bladder disease 3%. Eighty-eight percent of farmers had more than one of these diseases in their last crop. The duration of these crops are on average 2 months. Delaying the onset of feed training was significantly preventive for MAS (OR = 0.85, 0.75–0.95 95% CI) and BNP (OR = 0.88, 0.78–0.97), using iodine to disinfect water for BNP (OR = 0.23, 0.05–0.95), draining the pond sludge for parasitic disease (OR = 0.32, 0.10–0.97) and reducing time between filling the pond with water and stocking of fish for parasitic disease (OR of increasing time was 2.49, 1.13–6.40). Of all farmers interviewed, 43% used antibiotics preventively in fish food, but this practice was not significantly associated with lower disease prevalence. In a second study, fish from 48 randomly selected nursing ponds were sampled. Samples were randomly split to diagnose parasites (n = 443), common bacteria (n = 48 pools), or common fungi (n = 371). Prevalences of some pathogens were high, i.e. the parasite Trichodina, 48%, the bacteria Aeromonas hydrophila, causative for MAS, 23%, the bacteria Edwardsiella ictaluri, causative for BNP, 40%, the fungi Fusarium spp., causative for swollen swim bladder disease, 9.7%, and the fungi Aspergillus spp. 9.4%. The high prevalence of some of these diseases and pathogens is concerning, and shows that current preventive and mitigation measures need to be improved. The high number of crops with multiple diseases may indicate a reduced general resilience of the fish, which indicates that mitigation strategies would benefit from a comprehensive approach, instead of focused on single diseases or pathogens. Current preventive husbandry practices needs optimizing, but can play an important role in future mitigation strategies towards improved sustainability of striped catfish nursing farms.