<jats:title>Abstract</jats:title><jats:p>The relative fitness of drug resistant versus susceptible bacteria in an environment dictates resistance prevalence. Estimates for the relative fitness of resistant <jats:italic>Mycobacterium tuberculosis</jats:italic> (<jats:italic>Mtb</jats:italic>) strains are highly heterogeneous and mostly derived from <jats:italic>in-vitro</jats:italic> experiments. Measuring fitness in the field allows us to determine how the environment influences resistance spread.</jats:p><jats:p>We designed a household structured, stochastic mathematical model to estimate the fitness costs associated with multi-drug resistance (MDR) carriage in <jats:italic>Mtb</jats:italic> in 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-<jats:italic>Mtb</jats:italic> to 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-<jats:italic>Mtb</jats:italic> increased to 0.57 (0.43-0.73) when the fitness cost influenced both transmission and progression to disease equally.</jats:p><jats:p>We found the average relative fitness of MDR-<jats:italic>Mtb</jats:italic> circulating within households in Lima, Peru between 2010-2013 to be significantly lower than concurrent susceptible-<jats:italic>Mtb</jats:italic>. 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.</jats:p>