ABSTRACTObjectives: Adherence to nebulised treatment is typically low among people with cystic fibrosis (CF). This study sought to identify factors differentiating high or low nebuliser adherence patterns (i.e. ≥80% or <50% of all nebulised treatments over one year) among adults with CF.Design: A mixed methods cross-sectional exploratory comparison of low and high adherers to nebulised medications.Methods: Of 36 eligible adults invited from a UK CF centre, 20 were recruited (10 high, 10 low adherers). Adherence was objectively measured using electronic data capture. Participants completed a self-report questionnaire comprising measures of hypothesised predictors (habit, self-control, life chaos, perceived treatment burden, capability, motivation and opportunity), then took part in a semi-structured interview. Quantitative data were compared between groups, and interview data were thematically analysed.Results: High adherers reported stronger habit and greater opportunities, though habit and perceived opportunity scores were highly positively correlated. No other quantitative measure distinguished between groups. Habitual instigation tendency attenuated the relationship between treatment complexity and perceived treatment burden. Indeed, in interviews, high adherers reported that routinisation and greater automaticity made treatment burden more manageable.Conclusions: High adherers seized more opportunities for nebuliser use, adapted their lives more effectively to using nebulisers and were more likely to make nebuliser use habitual. Nebuliser adherence interventions among adults with CF might usefully target development of routines for instigating nebuliser use, and identification of opportune moments for nebuliser use.