Neisseria gonorrhoeae has a remarkable ability to develop resistance to all available therapeutic antimicrobials. This report describes the first four cases of verified failure to treat gonorrhoea using 1000mg cefathiamidine intramuscularly in Guangzhou, China; for each case, the patient was clinically cured after treatment with 500mg ceftriaxone intramuscularly. Enhanced monitoring of clinical treatment failures, finding new effective treatments and updating treatment guidelines are all of utmost importance to curb the spread of drug-resistant gonorrhoea.