The high proportion and factors contributing to self-medication with antibiotics in Guatemala City are similar in two disparate socio-economic pharmacies. In this setting, women come to the pharmacy more often than men in order to self-medicate and perceive little risk in its practice. Those of higher socio-economic status in Guatemala City are willing to speak to pharmacy personnel for advice regarding self-medication and, although future studies are necessary, this study sets the stage for future policy development regarding the role of the pharmacist in addressing self-medication with antibiotics. This type of role, however, may have a limited public health impact if there are no changes in the regulation of antibiotic promotion, sale and use in Guatemala.