Background: Accurate centre-level medication adherence measurement allows identification of highly performing CF centres, drives shared learning and informs quality improvement. Self-reported adherence is unreliable but data-logging nebulisers can capture objective data. However, adherence levels in current literature are limited by the use of agreed prescriptions and convenience sampling. In this single-centre retrospective study, we quantified the differences in centre-level adherence with different methods of calculating adherence (unadjusted vs normative adherence) and different data sampling frames (convenience sampling vs including difficult to obtain data). Methods: Adherence data were objectively captured using I-neb® from 2013-2016 in Sheffield Adult CF Centre. Adults on non data-logging devices, on ivacaftor or with previous lung transplantation were excluded. Adherence was calculated based on agreed regimen ('unadjusted adherence') or minimum required regimen ('normative adherence'). I-nebs® not brought to clinic were downloaded during home visits. Adults not on any inhaled therapy but with chronic Pseudomonas aeruginosa infection were included by counting their adherence as "0". Results: Of the 131 included adults, 126 provided I-neb® data. Calculating unadjusted adherence from I-nebs® brought to clinics resulted in the highest centre-level adherence (median 41.8% in 2013). Median adherence reduced after sequentially accounting for minimum required regimen (40.0% in 2013), I-nebs® not brought to clinics (32.9% in 2013) and adults not on any inhaled therapy (31.0% in 2013). Conclusions: Different approaches of calculating adherence produced different adherence levels. Adherence levels based only on agreed regimen among adults who readily brought their nebulisers to clinics can overestimate the effective adherence of CF centres.