DescriptionIntroduction: The work of breathing (WOB) imposed on the inspiratory muscles (IM) is elevated in cystic fibrosis (CF). Impaired inspiratory muscle strength (IMS) may contribute to dyspnea and exercise intolerance. Literature favors the preservation of (IMS) in adults with CF; however, this may misrepresent IM involvement due to the heterogeneity of study participants. Impaired IMS cannot be fully ruled out as the influence of disease severity has not been investigated. Clinical predictors of IMS in adults with CF are needed to identify individuals at risk for inspiratory overload. Purpose: The purpose of this study was to investigate the influence of disease severity on IMS and determine the potential for clinical measures to predict IMS in adults with stable CF. Methods: Maximal inspiratory pressure expressed in cmH2O (MIP) and percent of predicted (%MIP) was assessed to represent IMS in a cross-sectional sample of adults with stable CF. Between-group differences in MIP and %MIP were analyzed in adults with CF stratified by disease severity in comparison to healthy controls through general linear modelling. The ability for clinical measures to predict IMS was investigated through regression analysis. Results: Fifty-eight adults with CF and 20 healthy controls completed the study. IMS was decreased in advanced pulmonary disease. Dyspnea was associated with MIP (r=-0.48, p<0.001) and %MIP (r=-0.50, p<0.001). Disease severity accounted for 23% of the variance seen in MIP and %MIP after controlling for confounding variables (p<0.001). Resultant linear models explained 43% of the variance in MIP and 52% in %MIP. Conclusions: Disease severity negatively influences IMS in adults with CF and impaired IMS can be missed when not controlling for the degree of airway obstruction. Decreased IMS is apparent in the presence of advanced CF-related lung disease though select individuals may be protected against this impairment. A combination of pulmonary, nutritional, and demographic factors may identify adults with CF at risk for inspiratory overload in need of IM testing. The clinical significance of these findings should be determined through prospective studies. Future research on the IM in CF must control for disease severity or risk misrepresenting the influence of CF lung disease.