OBJECTIVE: Malnutrition in cystic fibrosis (CF) is associated with poorer survival, but the determinants of fat-free mass (FFM) depletion are not well-characterized. It is unknown whether routine nutritional indicators, including body mass index (BMI), are adequate for detecting FFM depletion. This study aimed to determine the prevalence of FFM depletion in adults with CF, to compare fat-free mass index (FFMI) with BMI, and to identify predictors of FFM depletion. METHODS: This was a prospective cross-sectional study of 86 adults with CF (19-59 y old). Body composition was assessed using dual-energy X-ray absorptiometry to determine FFMI and BMI. FFMI percentiles and Z-scores were derived from a reference population of 156 healthy adults. FFM depletion was defined as an FFMI below the fifth percentile for age and gender and low BMI as <18.5 kg/m(2). Univariate and multivariate analyses identified predictors of FFMI and FFMI Z-score. RESULTS: Mean FFMIs were 18.3+/-1.9 kg/m(2) in men with CF and 15.8+/-1.1 kg/m(2) in women with CF (P<0.0005). FFM depletion was found in 14% of adults with CF, and low BMI was found in 18.6%. The sensitivity of BMI for detecting FFM depletion was 42%. Forced expiratory volume in 1 s as a percentage of predicted was independently associated with FFMI in women (r=0.62, P<0.0001) and men (r=0.28, P=0.045) and FFMI Z-score (r=0.41, P<0.0001). CONCLUSION: FFM depletion was found in 14% of adults with CF, but was undetectable by BMI in 58% of these patients. These findings, together with the association of FFMI with forced expiratory volume in 1 s predicted, suggest a role for body composition assessment in adult CF care.