Author summary Why was this study done? Shortening antibiotic treatment duration is a commonly adopted antibiotic stewardship strategy, with the expectation that it will reduce antimicrobial resistance in treated individuals and in the overall population. Antibiotic selective pressure acts predominantly on “bystander” colonising bacteria for resistance, and this depends on the spectrum of coverage, pharmacokinetic and pharmacodynamic properties of individual antibiotics. Empirical evidence and an understanding of the mechanisms by which antibiotic treatment duration effects the emergence and spread of antimicrobial resistance are lacking. Understanding the key factors driving the effect of antibiotic treatment duration on resistance carriage will help to inform future research study designs, antimicrobial stewardship interventions, and resource allocation in multimodal control strategies. What did the researchers do and find? We modelled within- and between-host dynamics of colonising “bystander” susceptible and resistant bacteria in response to systemic antibiotic treatment and compared the model findings with a systematic review and meta-analysis. The meta-analysis found one additional antibiotic treatment day is associated with a 7% absolute increase in risk of resistance carriage when antibiotics administered were not effective against the resistance phenotype in the colonising bacteria. For treated individuals, the models showed that shortening antibiotic treatment duration is most effective at reducing resistance carriage when resistant bacteria grow rapidly under antibiotic selection pressure and decline rapidly when stopping treatment. At a population level, shortening antibiotic treatment duration is most effective at reducing resistance carriage in high transmission settings. Shortening antibiotic treatment duration may increase resistance carriage when the antibiotics administered are effective at eliminating colonising bacteria with a particular resistance phenotype. What do these findings mean? Shortening antibiotic treatment duration may increase or decrease colonisation by resistant bacteria, dependent upon individual and combined bacterial and antibiotic characteristics. The effect of shortening antibiotic treatment duration on colonisation by resistant bacteria colonisation is potentially modest due to short hospitalisation periods and slow decolonisation of resistant bacteria. These findings can inform antibiotic stewardship programmes to shorten antibiotic treatment and infection prevention and control policies to reduce transmission of resistant bacteria.