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Background While rural health guidelines have often cautioned against digital interventions due to infrastructure and literacy barriers, this study introduces an SMS-based conversational artificial intelligence (CAI) that overcomes these limitations to promote HPV vaccination.Objective To evaluate an SMS-based CAI using the Centers for Disease Control (CDC)’s presumptive and CASE (Corroborate, About Me, Science and Explain) frameworks to promote HPV vaccination among rural parent-adolescent dyads by: (1) testing its usability; (2) assessing the feasibility of co-design with clinicians and parent-adolescents; (3) identifying adoption barriers and (4) examining communication preferences across behavioural profiles.Methods We developed a CAI simulator using the presumptive approach and the structured CASE method to address 11 common concerns about the HPV vaccine. A multimethod usability study with 13 rural parent-adolescent dyads (n=26) included in-depth interviews and the System Usability Scale.Results The CAI achieved excellent usability (mean SUS 85.2, ~96th percentile). A previously undocumented behavioural profile—vaccine-unaware—was identified, distinct from hesitancy, and best addressed through empathetic, exploratory dialogue. Key adoption barriers included integration with existing preventive care routines and endorsement by trusted local providers.Conclusions Contrary to the assumption that rural residents resist digital tools, participants engaged readily when content was credible, locally endorsed and accessible via SMS. Findings highlight the conditional effectiveness of the CDC’s presumptive style in CAIs—well-suited for vaccine-compliant users but less effective for sceptical or unaware groups, who, we argue, would respond better to conversational, empathetic tones.