Background Self-medication with antibiotics is a common practice, which may lead to the development of antimicrobial resistance (AMR)—a major health concern worldwide. The most common reason for the development of AMR is a lack of education and regulatory policies and the lack of community pharmacists.

Objective To assess various factors that lead to self-medication with antibiotics, which might cause AMR and hinder effective healthcare.

Methods A cross-sectional study was carried out using a predesigned questionnaire to collect data from 800 respondents. The respondents were selected by simple random sampling during November 2014 to January 2015 from different regions of Khyber Pakhtunkhwa (KPK), Pakistan. Only properly completed questionnaires were assessed for different variables. The collected data were analysed using SPSS V.16.

Results 527 people completed and returned the questionnaire—a response rate of 66%. Self-medication with antibiotics was reported by 135 participants (26%), with a higher prevalence of men than women (48% vs 38%, respectively). The main reason for self-medication was previous experience with the same antibiotic (68%). The most commonly used antibiotics were amoxicillin-clavulanate (40%) and major indications for self-medication were sore throat (29%) and flu (24%). Of the 527 respondents, only 104 (20%) were aware of AMR.

Conclusions This study is the first to evaluate self-medication with antibiotics in KPK, Pakistan. In view of the high prevalence of self-medication, introduction of a public health policy through drug regulatory authorities, public awareness programmes/campaigns, patient education about AMR and appropriate use of antibiotics are critically required. The role of community pharmacists needs to be strengthened.