Abstract Background The elastinolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage. Cystatin C, an inhibitor of these enzymes, is expressed in arterial smooth muscle cells; an imbalance in cystatin C has been implicated in the aortic wall degeneration observed in abdominal aortic aneurysms (AAAs). The aim of the study was to investigate the impact of a polymorphism in the signal peptide of the cystatin C gene on the growth of small AAAs. Methods Some 424 patients with a small AAA (4·0–5·5 cm) were monitored for AAA growth by ultrasonography and provided a DNA sample for analysis of the + 148 G > A polymorphism in the cystatin C signal peptide and the—82 G > C polymorphism in the gene promoter. The median length of follow-up was 2·8 years and AAA growth rates were calculated by linear regression analysis. Results For patients of + 148 GG (n = 263), GA (n = 147) and AA (n = 20) genotypes, the mean(s.d.) AAA growth rates were 0·37(0·29), 0·37(0·23) and 0·30(0·26) cm, and initial diameters were 4·58(0·35), 4·58(0·35) and 4·62(0·36) cm, respectively. Patients of + 148 AA genotype had a slower aneurysm growth rate (unadjusted P = 0·058; after adjustment for age, sex, initial AAA diameter and smoking, P = 0·027). There also was a trend for the rare homozygotes of the—82 C allele to have slower AAA growth (adjusted P = 0·055). Smoking history had a stronger association with aneurysm growth (P = 0·003). Conclusion There was a weak association between variation in the cystatin C gene and AAA growth. Medical strategies to limit AAA growth might include the inhibition of cysteine proteases.