Twenty-three years after the discovery of the CFTR gene, more than 1900 anomalies are described in the world, the majority of them being single base-pair substitutions or micro-insertions/deletions. Identification of mutations has important implications for genetic counselling, prenatal diagnosis, cascade screening in families, as well as for understanding the genotype–phenotype relationship. Since a few years, NGS technologies enable us to overcome the classical approaches of whole coding sequence sequencing at single nucleotide resolution. The aim of our study is to compare 3 different strategies with the Ion Torrent technology (Life Technologies, LT): Ampliseq (LT), Haloplex (Agilent) and homemade Long Range PCR (LR). Preliminary results showed that the coverage of the CFTR locus by Ampliseq is limited to 51% and includes 86% of exons with a depth generally consistent between amplicons. Haloplex approach gives more heterogeneous depth and coverage. Finally, LR-PCR showed coverage consistent with the design but differences at depth between each LR amplification. The development of libraries by the two first approaches is rapid (less than 24 h) and technically easy. For LR-PCR, It takes about two days to build a library with long and time-consuming manual steps. Sequencing result for the CFTR gene were validated with wild-type samples and DNA carrying known variants (mutations and polymorphisms) previously identified by DHPLC, HRM and sequencing. In conclusion, the sequencing of the entire CFTR locus by NGS is a tool that can quickly respond to issues such as prenatal diagnostic and the most promising approach seems to be the LR strategy.