BACKGROUND: Historically, studies of adherence to airway clearance therapy in cystic fibrosis (CF) have relied on self-reporting. We compared self-reported airway clearance therapy adherence to actual usage data from home high-frequency chest wall compressions (HFCWC) vests and identified factors associated with overestimation of adherence in self-reports. METHODS: Pediatric patients who perform airway clearance therapy with a HFCWC vest were eligible to participate. Objective adherence data were obtained from the HFCWC device, which records cumulative utilization time. Two readings at least 5 weeks apart were collected. Objective adherence was recorded as a ratio of mean-to-prescribed daily use (%). Self-reported adherence data were collected with a caregiver survey at enrollment. Adherence rates were categorized as low (< 35% of prescribed), moderate (36 –79% of prescribed), and high (> 80% of prescribed). An overestimation was present when self-reported adherence was at least one category higher than objective adherence. RESULTS: In the final sample (N ± 110), mean adherence by usage data was 61%. Only 35% of subjects (n ± 38) were highly adherent, and 28% (n ± 31) were low adherent. In contrast, 65% of subjects (n ± 72) reported high adherence and only 8% (n ± 9) reported low adherence (P < .001). Nearly half of self-reports (46%) overestimated adherence. In a multiple regression analysis, overestimation was associated with multiple airway clearance therapy locations (odds ratio 7.13, 95% CI 1.16 – 43.72, P ± .034) and prescribed daily use > 60 min (odds ratio 3.85, 95% CI 1.08 –13.76, P < .038). Among subjects with prescribed daily airway clearance therapy > 60 min, the odds of overestimating adherence increased 3-fold (odds ratio 3.04, 95% CI 1.17–7.87, P ± .02) in a lower-income (< $50,000/y) environment. CONCLUSIONS: Self-reports overestimated actual adherence to airway clearance therapy, and the overestimation increased with treatment occurring in multiple households and prescribed therapy duration. Among participants with prescribed airway clearance therapy > 60 min, overestimation increased with lower income. Objective measures of adherence are needed, particularly for lower-income children and those receiving treatments in multiple locations.