Background/Aims: The Hp<sup>1</sup> /Hp<sup>2</sup> DNA polymorphism has previously been implicated in susceptibility to diabetic nephropathy in some but not all studies. In an attempt to clarify these conflicting findings, we conducted a case-control association study in a Caucasian population. Methods: We recruited 224 and 285 type 1 diabetic patients with (cases) and without (controls) nephropathy, respectively, from 2 centres based in Northern Ireland and the Republic of Ireland. Hp<sup>1</sup> /Hp<sup>2</sup> genotyping was performed using a combination of long-range and multiplex PCR. Allele and genotype frequencies in cases and controls were compared using the χ<sup>2</sup> test. Results: There was a statistically significant increase in the frequency of the Hp<sup>2</sup> allele in cases compared to controls (65.6 vs. 58.6%, OR = 1.35, 95% CI: 1.04–1.76, p = 0.03). The distributions of genotypes were in Hardy-Weinberg equilibrium for both cases and controls, and the overall frequency of the Hp<sup>1</sup> allele was 38.3%, which is similar to that found in other Western European populations. Conclusions: The results suggest that the Hp<sup>2</sup> allele may confer susceptibility to nephropathy in patients with type 1 diabetes.