Immunochemical faecal occult blood tests (I-FOBT) detect more effectively advanced neoplasia than guaiac tests (G-FOBT). The study aim was to compare the performance of an I-FOBT whilst varying the positivity threshold and considering four analysis modalities: one sample was performed (MG(1)), two samples were performed and at least one sample was positive (MG(2+)), both samples were positive (MG(2++)) or the mean of the two samples' log-transformed haemoglobin contents exceeded the cutoff (MG(2m)). Screening for colorectal cancer using both G-FOBT and two samples' I-FOBT was performed by an average-risk population sample of 20,322 subjects. Among the 1,615 subjects with at least one positive test, 1,277 had a satisfactory colonoscopy result; 43 invasive cancers and 270 high-risk adenomas were detected. The I-FOBT was reinterpreted under each analysis modality (a random selection of one sample led to MG(1)). For all modalities, increasing the positivity threshold decreased sensitivity and increased specificity. The relative ROC curves (in reference to G-FOBT) demonstrated similar performance for MG(1) and MG(2+), and improved performance for MG(2m). MG(2++) sensitivity was limited within the range of positivity thresholds evaluated. For any specificity, MG(2m) provided the highest sensitivity. For any sensitivity, MG(2m) provided the highest specificity. For any positivity rate, MG(2m) provided both the highest sensitivity and specificity. This study suggests the replacement of MG(2+) by MG(1) or, for even better performance, by MG(2m) provided that two samples are performed with similar participation (which should be explored). The targeted positivity rate could then be achieved by choosing the positivity threshold.