Background: Atherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance. Methods: A total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty?eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein?associated phospholipase A2 (Lp?PLA2) in each group were detected, and the related risk factors were also statistically analyzed. Results: Fibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]:22.242, 95% confidence interval [CI]: 6.458–76.609, P < 0.001) with the largest absolute value of the standardized partial regression coefficient B(b: 1.079). Lp?PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236–35.837, P < 0.001) with b = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95%CI: 4.022–58.250, P < 0.001) with b = 1.026. Conclusions: Fbg, Lp?PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.