Background <p>Antibiotic resistance (ABR) is a global health threat, significantly driven by its misuse. The World Health Organization stresses the need for better antibiotic use to combat ABR through behavioral change interventions. Visual storytelling, which merges narrative with visuals, can enhance health behaviors by boosting cognitive and emotional engagement. In Pakistan, more than half of the population lack access to mobile phone, limiting digital health solutions. To address this gap, we developed a culturally tailored Visual Storytelling for Antibiotic Adherence (VISTA) intervention – a theory-driven sticker-based tool – to improve antibiotic adherence among urinary tract infection (UTI) patients in low-connectivity settings.</p> Methods <p>In this parallel, two-arm superiority randomized controlled trial, participants with physician-confirmed uncomplicated UTI who have filled an oral antibiotic prescription will be recruited from six tertiary care hospitals in Khyber Pakhtunkhwa, Pakistan. The participants will be randomized in a 1:1 manner to receive either the VISTA intervention or standard care. The VISTA intervention was developed based on nudge theory, guided by the Taxonomy of Choice Architecture framework, and complemented by the MINDSPACE (messenger, incentives, norms, defaults, salience, priming, affect, commitments, and ego) framework. It was developed and validated through a Delphi method, assessing expert feedback, and refined based on a patient understanding study. The intervention sticker uses contrasting colors—red (non-adherence: bacteria evolving into “superbugs”) and green (adherence: antibiotics fully eradicating bacteria)—to communicate the consequences of incomplete versus complete adherence. The primary outcome is adherence, measured by pill count at the initial follow-up. Secondary outcomes include UTI recurrence, knowledge, and attitudes regarding antibiotic adherence. Analysis will follow both intention-to-treat and per-protocol principles.</p> Discussion <p>This randomized controlled trial will evaluate a theory-driven, scalable intervention for low-resource, low-connectivity settings, aligning with WHO priorities for ABR mitigation. It addresses the patient support gap caused by limited digital access. Pill counts provide an objective adherence measure, though they may miss intentional non-adherence; including UTI recurrence as a secondary outcome helps mitigate this. Cultural tailoring through expert panels and patient feedback aims to enhance relevance and applicability across similar contexts, improving generalizability.</p> Trial registration <p>The trial was registered with ClinicalTrials.gov (registered: March 13, 2025, NCT06885658, <a href="https://clinicaltrials.gov/study/NCT06885658">https://clinicaltrials.gov/study/NCT06885658</a>).</p>