Compared with the guaiac-faecal occult blood test (gFOBT), faecal immunological tests (FIT) are considered to be more effective for colorectal cancer (CRC) screening. However, only scarce research has examined the outcomes of switching to FIT within a mature gFOBT-based CRC screening programme. We reported a 15-year experience of biennial FOBT screening in a well-defined population of approximately one million inhabitants, including six gFOBT-based screening rounds and one round with FIT at the 30 μg Hb/g cut-off. The main outcome measures were screening participation, FOBT positivity and advanced neoplasia detection in each round. In this study, 647 676 screenings were performed in 228 716 different individuals, leading to 17 819 positives and 16 580 follow-up colonoscopies. Compared with the last gFOBT round, switching to FIT led to an increased participation of nearly 20% points, and a fivefold increased detection of CRC and advanced adenoma among invitees (3-fold among attendees). The numbers needed to screen and scope to detect one advanced neoplasia declined from 221 to 66 and from 4.7 to 2.6, respectively. The present population-based study demonstrated a dramatical increase in the diagnostic yield of advanced neoplasia by switching to FIT within a mature gFOBT-based CRC screening programme.