Background The high blood homocysteine (Hcy) levels found in patients with hyperhomocysteinemia (HHcy) have been implicated in an increased risk of cardiovascular disease morbidity and mortality in end-stage renal disease (ESRD). This study investigated the association of HHcy with progression of IgA nephropathy. Methods We analyzed 108 participants newly diagnosed with IgA nephropathy between August 2005 and August 2007 in the Department of Nephrology, Chinese People's Liberation Army General Hospital. The association between clinicopathological factors and the Hcy levels were analyzed by Logistic regression and those with ESRD risk were analyzed by Cox regression. Results Patients were aged (35.71±10.73) years and included 45.71% women and 12.04% patients with HHcy. In multivariate Logistic regression analysis, HHcy was associated with arterial lesions (OR 2.60; 95% CI 1.55-4.34; P<0.001) even when age, body mass index, estimated glomerular filtration rate, mean arterial pressure, and initial proteinuria were taken into account. Mean follow-up was (67.37±16.21) months. HHcy was also associated with worse ESRD-free survival (HR 4.71; 95% CI 1.45 to 15.31; P=0.010). Conclusion HHcy is associated with the risk of intrarenal arterial lesions and may be useful for estimating the prognosis of IgA nephropathy. Chin Med J 2014;127 (10): 1849-1852