BACKGROUND: Magnesium is one of the most important minerals in the body. Although some studies reported that patients with cystic fibrosis (CF) lack magnesium, no international study has assessed the importance of oral magnesium supplementation in CF patients. OBJECTIVE: We prospectively investigated the long-term effect of oral magnesium supplementation on respiratory muscle strength by using manuvacuometry and the Shwachman-Kulczycki (SK) score among children and adolescents with CF. DESIGN: This double-blind, randomized, placebo-controlled crossover study included 44 CF patients (aged 7-19 y; 20 males) who were randomly assigned to receive magnesium (n = 22; 300 mg/d) or placebo (n = 22) for 8 wk with a 4-wk washout period between trials. All patients were undergoing conventional treatment of CF. The experimental protocol included clinical evaluation, assessment of urinary concentration of magnesium, and manuvacuometric measurements [maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP)]. MIP was the primary outcome. RESULTS: Urinary magnesium increased after the administration of magnesium (change: 36.38 mg/d after magnesium compared with 0.72 mg/d after placebo; P < 0.001). Moreover, MIP and MEP significantly improved only after magnesium administration (change in MIP: 11% predicted after magnesium compared with 0.5% predicted after placebo; change in MEP: 11.9% predicted after magnesium compared with 0.8% predicted after placebo; P < 0.001 for both). Magnesium administration had a beneficial effect on clinical variables assessed by the SK score (change: 4.48 points after magnesium compared with -1.30 points after placebo; P < 0.001). CONCLUSION: Oral magnesium supplementation helped improve both the SK score and respiratory muscle strength in pediatric patients with CF.