Introduction: Many colonoscopies following a positive fecal immunochemical test (FIT) will not identify a probable cause for fecal blood, and missed neoplasia is a concern. The study determined whether the absence of neoplasia at a FIT positive diagnostic colonoscopy was due to a missed lesion and whether the initial FIT hemoglobin (f-Hb) concentration could predict missed lesions. Methods: This was a retrospective audit of patients who had undergone diagnostic colonoscopy after FIT screening (2 sample ≥ 20 µg Hb/g feces). Probable bleeding lesions including cancer, advanced adenoma, colitis, and angiodysplasia were considered a “positive colonoscopy outcome.” For those with a negative outcome, findings at the subsequent colonoscopy were assessed. Results: There were 1087 good quality colonoscopies within 12 months of a positive FIT. In total, 171 (15.7%) patients had a positive outcome at the diagnostic colonoscopy. Subsequent colonoscopies of negative outcome cases (n = 418, median of 3.1y later) were reviewed; of these, there were 57 (13.6%) cases with a positive outcome. This included CRC in 0.5% (n = 2) and advanced adenoma in 11.7% (n = 49). High f-Hb and having both FIT samples ≥ 20 µg/g feces were associated with a positive outcome at the original diagnostic colonoscopy (p < 0.05). However, f-Hb was not predictive for a positive outcome at the subsequent colonoscopy by either maximum f-Hb (p = 0.768), total f-Hb (p = 0.459), or both FIT samples ≥ 20 µg/g (p = 0.091). Conclusion: A small proportion of “false” positive FIT results had cancer or advanced adenoma found at the subsequent colonoscopy. A missed lesion could not be predicted by the initial FIT f-Hb.