OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD ( < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants ( < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 ( = 0.001) and decreased CFH ( < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 ( = 0.034), elevated AP50 ( < 0.001), decreased CFH ( < 0.001), increased age ( = 0.011) and increased BMI ( = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 ( = 0.017), elevated AP50 ( = 0.023), decreased CFH ( = 0.005) and increased age ( = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.