Abstract The relative fitness of drug resistant versus susceptible bacteria in an environment dictates resistance prevalence. Estimates for the relative fitness of resistantMycobacterium tuberculosis(Mtb) strains are highly heterogeneous and mostly derived fromin-vitroexperiments. Measuring fitness in the field allows us to determine how the environment influences resistance spread. We designed a household structured, stochastic mathematical model to estimate the fitness costs associated with multi-drug resistance (MDR) carriage inMtbin Lima, Peru between 2010-2013. By fitting the model to data from a large prospective cohort study of TB disease in household contacts we estimated the fitness, relative to susceptible strains with a fitness of 1, of MDR-Mtbto be 0.33 (95% credible interval: 0.17-0.54) or 0.39 (0.26-0.58), if only transmission or progression to disease, respectively, was affected. The relative fitness of MDR-Mtbincreased to 0.57 (0.43-0.73) when the fitness cost influenced both transmission and progression to disease equally. We found the average relative fitness of MDR-Mtbcirculating within households in Lima, Peru between 2010-2013 to be significantly lower than concurrent susceptible-Mtb. If these fitness levels do not change, then existing TB control programmes are likely to keep MDR-TB prevalence at current levels in Lima, Peru.