Aim: In guaiac faecal occult blood test (gFOBT) screening at least 50% of positive individuals will have a colonoscopy negative for colorectal neoplasia. The question of continuing screening in this group has not been addressed. Method: Data on participants aged 50-69 years with a positive gFOBT result and a negative colonoscopy were followed through the biennial screening pilot conducted between 2000 and 2007 in Scotland. Results: In the first screening round, 1527 colonoscopies were negative for neoplasia. 1300 were re-invited in the second round, 905 accepted, and 157 had a positive gFOBT result giving a positivity rate of 17.4%. Colonoscopy revealed 20 subjects with adenoma and six with invasive cancer. 1031 were invited for a third time in the third screening round and 730 accepted: 55 had a positive gFOBT test, giving a positivity rate of 7.5%. In this group, six colonoscopies revealed adenomas but there were no cancers diagnosed. In the third screening round, 108 individuals had had two positive gFOBT results and two subsequent negative colonoscopies. 84 were invited for a third gFOBT, 66 accepted and 19 (25.6) had a positive result none of whom had an adenoma or carcinoma. Conclusion: These data indicate that a negative colonoscopy following a positive gFOBT is not a contraindication for further screening, although this is likely to have a low yield of neoplastic pathology after two negative colonoscopies.