We report on the first six cases of acquired resistance to bedaquiline in Pakistan.  Seventy sequential culture isolates from 30 drug-resistant tuberculosis patients on bedaquiline-containing regimen were tested for minimum inhibitory concentration(MIC) and whole genome sequencing. An increase in MICs associated with cross-resistance to clofazimine and appearance of specific mutations was documented in six cases. The study underlines that appropriate monitoring is mandatory for the introduction of new drugs.