Antimicrobial drug resistance in Neisseria gonorrhoeae has been documented worldwide; however, the situation in Sub-Saharan Africa has received little attention. It is critical to establish diagnostics and extend surveillance to prevent the emergence of illnesses resistant to multiple treatments. Monitoring antimicrobial susceptibility is crucial to gather data that can inform treatment recommendations, resulting in effective therapy, reduced gonorrhea-related complications and transmission, and efficient treatment. Government authorities may set research and preventive objectives, as well as treatment recommendations, using data from the Gonococcal Antimicrobial Surveillance Program (GISP). Local and state health authorities may use GISP data to make decisions about the allocation of STI prevention services and resources, to guide preventive planning, and to disseminate information about the most successful treatment practices. Using molecular and culture approaches, we investigated the occurrence of antibiotic resistance in isolates from KwaZulu Natal, South Africa. The majority of gonococcal isolates (48 %) showed absolute resistance to ciprofloxacin, with penicillin and tetracycline resistance rates of 14 % each. Only one gonococcal isolate tested positive for azithromycin resistance, with a minimum inhibitory concentration (MIC) of 1.5 µg/mL. Ceftriaxone was effective against all gonococcal isolates tested.