Striped catfish (Pangasianodon hypophthalmus) is the dominant aquacultured species in the Mekong Delta and Vietnam exports frozen fillets worldwide. Bacillary Necrosis of Pangasius (Edwardsiella ictulari) and hemorrhagic disease (Aeromonas hydropila) are the main diseases in striped catfish and responsible for a widespread use of antimicrobials (AMU). This study was conducted to better understand AMU practices of striped catfish farmers with a long-term aim to suggest better disease prevention and control measures with reduced needs for AMU. A total of 90 small- (45 < 3 ha size) and large-scale (45 > 3 ha size) striped catfish farm owners were questionnaire interviewed in An Giang, Dong Thap and Can Tho provinces to obtained information about their fish health management practices, in particular chemical and antimicrobial usage. Farmers experienced between 2 and 10 disease outbreaks mainly during the first three-month’s growth period. Most farmers (90-100%) used between one to five different classes of antimicrobials for disease treatment. Nine to 15 different classes of antimicrobials were used by farmers to prepare their medicated feed sometimes in combination (e.g. doxycycline/amoxicillin). Small-scale farmers more often administered antimicrobial treatment and used a higher number of different antimicrobial classes compared to large-scale farmers. The most commonly used antimicrobials irrespective of farm size were doxycycline (44.4-61.1%%) and amoxicillin (33.3-53.3%). Both small- and large-scale farmers reported the use of enrofloxacin despite this drug being banned for use in aquaculture in 2012. Several farmers experienced that antimicrobial treatment was not effective and they therefore had to use different antimicrobials. There is an urgent need to monitor and communicate to farmers the antimicrobial susceptibility of the two main bacterial pathogens in striped catfish so effective treatment guidelines can be established. Also, studies are needed to obtain information about challenges and problems with applying the commercial vaccine that protects against the two bacterial diseases so this and other future vaccines will be used more widely by striped catfish farmers and thereby significantly reducing the need to use antimicrobials.