Background: Nontuberculous mycobacterium (NTM) is a rare cause of prosthetic joint infection (PJI) following primary total knee arthroplasty (TKA). NTM causes a variety of infections, mainly divided into pulmonary and extrapulmonary infections. In Pakistan, there was a 7.7-fold increase in NTM infections from 21 cases in 2012 to 163 cases in 2018. An earlier study evaluating the distribution of NTM species across Pakistan suggested geographical variation across different regions, every area having its own distribution spectrum. There are no data available especially in developing countries such as Pakistan regarding PJI due to NTM following primary TKA. The purpose of our study was to determine treatment outcomes of two-stage revision surgery following NTM infection. Methods: This is a retrospective study. Patients who underwent TKA between June 2008 and December 2018 were included in the study. NTM was defined as the presence of traditional criteria for diagnosing PJI plus growth of NTM cultured from a joint aspirate or deep periprosthetic tissue specimen using Löwenstein-Jensen medium and Mycobacteria Growth Indicator Tube medium. All patients were female with a mean age of 62.8 ± 7.9 years. The mean body mass index was 25.6 ± 2.8 kg/m². Treatment outcomes were categorized into favorable and unfavorable. Results: We found rapid-growing mycobacterium in 6 patients whereas slow-growing mycobacterium was found in 2 patients only. Generally, clarithromycin was the standard antibiotic used in all cases of NTM infections. All patients underwent revision surgery. Conclusions Meticulous surgical debridement and prolonged antibiotic treatment course were the only hope of cure to combat the unusual cause of PJI following primary TKA.