Multidrug-resistant tuberculosis (MDR-TB) has hampered global efforts to control and manage tuberculosis infections. Indonesia is no exception, ranking 8th globally among high MDR-TB burden countries. WHO estimates that about 2% of new and 17% of retreatment cases in Indonesia test positive for multi-drug resistance. The US Global Health Initiative strategy for Indonesia aims to support Indonesia’s effort to diagnose one million TB patients and diagnose and treat 5,100 MDR-TB patients by 2015. Though some ground has been gained in partnership with the Indonesia National TB Program, there is still much work to be done in reaching these targets. Major gaps exist on in our understanding how and under what circumstances resistant Mtb emerges and is transmitted. This project thus aims to elucidate the host, microbial, and environmental factors that underlie the emergence and transmission of MDR and XDR-TB in Indonesia. This project aims to obtain an unbiased prevalence of MDR in this community and to describe the distribution and patterns of drug resistance mutations in this population. This is an observational prospective cohort study. During the study’s 24-month enrollment period, 2,400 incident cases of suspect pulmonary tuberculosis registered at any government-operated community health centers, lung clinic, or hospital located within Padang, Pariaman Regency, and Pariaman City districts’ geographic catchment areas will be enrolled. Participants will be followed-up by their health care professional as per routine national protocol. Participants testing positive for RIF-resistance will have samples cultured, tested for antibiotic resistance, and sent for whole genome sequencing. The results of this study will help the NTP and USAID accurately assess the burden of MDR and assess the need for new TB diagnostics and second line drugs within Indonesia. The identification of specific lineages and MDR mutations in our region will potentially allow us to optimize diagnostics to accommodate local difference in TB strain biology.