Immunochemical faecal occult blood tests have shown a greater sensitivity than guaiac test in colorectal cancer screening, but optimal number of samples and cutoff have still to be defined. The aim of this multicentric study was to evaluate the performance of immunochemical-based screening strategies according to different positivity thresholds (80, 100, 120 ng ml(-1)) and single vs double sampling (one, at least one, or both positive samples) using 1-day sample with cutoff at 100 ng ml(-1) as the reference strategy. A total of 20 596 subjects aged 50-69 years were enrolled from Italian population-based screening programmes. Positivity rate was 4.5% for reference strategy and 8.0 and 2.0% for the most sensitive and the most specific strategy, respectively. Cancer detection rate of reference strategy was 2.8 per thousand, and ranged between 2.1 and 3.4 per thousand in other strategies; reference strategy detected 15.6 per thousand advanced adenomas (range=10.0-22.5 per thousand). The number needed to scope to find a cancer or an advanced adenoma was lower than 2 (1.5-1.7) for the most specific strategies, whereas it was 2.4-2.7, according to different thresholds, for the most sensitive ones. Different strategies seem to have a greater impact on adenomas rather than on cancer detection rate. The study provides information when deciding screening protocols and to adapt them to local resources.