AbstractBackgroundUrban informal settlements have been described as the epicenters of frequent antibiotic misuse, which has local and global consequences on the goals of antimicrobial stewardship. The aim of this study was to assess the relationship between knowledge, attitude, and practices of antibiotic use among households in urban informal settlements in the Tamale metropolis of Ghana.MethodThis study was a prospective cross‐sectional survey of the two major informal settlements in the Tamale metropolis, namely Dungu‐Asawaba and Moshie Zongo. In all, 660 households were randomly selected for this study. Households with an adult and at least a child under 5 years old were randomly chosen. An adult with knowledge of household healthcare practices was selected  to respond to a structured questionnaire.ResultsIn all, 291 (44.1%) of the 660 households reported taking at least one type of antibiotic within the last month before the study and 30.9% (204/660) had used antibiotics without a prescription. Information on which antibiotics to use was obtained mostly from friends/family members 50 (24.5%) and were commonly purchased from a medical store or a pharmacy 84 (41.2%), saved up from a previously used antibiotic 46 (22.5%), a friend/family members 38 (18.6%), and drug hawkers 30 (14.7%). Amoxicillin 95 (26.0%) was the most frequently used antibiotic and the commonest indication for antibiotics use was diarrhea 136 (37.9%). Female respondents (odds ratio [OR] = 3.07; 95% confidence interval [CI] = 2.199–4.301;p< 0.0001), larger households (OR = 2.02; 95% CI = 1.337–3.117;p= 0.0011) and those with higher monthly household income (OR = 3.39; 95% CI = 1.945–5.816;p< 0.0001) were more likely to have good knowledge of appropriate antibiotic use and antibiotic resistance. Furthermore, bad attitudes influenced participants' use of antibiotics without prescription (OR = 2.41; 95% CI = 0.432–4.05;p= 0.0009).ConclusionThis study exposes the drivers of inappropriate use of antibiotics at the household level, particularly in urban informal settlements. Policy interventions aimed at controlling the indiscriminate use of antibiotics in such settlements could improve the responsible use of antibiotics. Keywords: antibiotic resistance, informal settlements, Tamale, Ghana