Summary Background The 6 min walk test (6MWT) provides prognostic information in various respiratory diseases, but limited data exist in cystic fibrosis (CF) adults. Methods Consecutive CF adults who performed 6MWT at Cochin Hospital (Paris, France) over 12 years were analyzed. The cut-off 6 min walking distance (6MWD) value that best predicted a combined endpoint (death without transplant or lung transplant) was established using a receiver operating curve. Determinants of low 6MWD or of desaturation (SpO2 ≤ 90%) during 6MWT were examined using multivariate logistic regressions. Prognostic value of these variables was assessed using Kaplan–Meier and Cox analyses. Results 6MWT was performed in 286 CF adults (median: age, 28 yr; FEV1, 45% predicted) of whom 14% (n = 40) had lung transplant and 6% (n = 18) died without transplant. 6MWD correlated with FEV1% predicted (r = 0.43; P < 0.001), but markedly differed in subjects within the same range of FEV1. A 6MWD ≤475 m predicted death or transplant and was mostly found in patients with FEV1 ≤60% predicted. Desaturation during the 6MWT occurred in 29% of patients, exclusively in subjects with FEV1 ≤60% predicted. Both 6MWD ≤475 m and desaturation during the 6MWT were independent predictors of death or transplant. Conclusion The 6MWT provides prognostic information in CF adults, especially in subjects with FEV1 ≤60% predicted.