Aim To determine whether the low C-peptide levels (<50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance. Methods We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series (n=1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA1c control (n=1273), as well as diabetic complications (n=324) and presence of hypoglycaemia (n=323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker. Results C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset (P<0.0001), after adjusting for disease duration. C-peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P=0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA1c (P<0.0001). Severe hypoglycaemia was associated with the lowest C-peptide levels compared with mild (P=0.049) or moderate (P=0.04) hypoglycaemia. All levels of measurable C-peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5-Anhydroglucitol (P<0.0001). Conclusions Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes.