High level of C-reactive protein (CRP), most popular inflammatory marker, increases the risk of thrombotic cardiovascular events. Aspirin, which has both anti-inflammatory and anti-thrombotic effects, has the potential to influence CRP release. Several studies have been reported investigating clinical effects of aspirin on CRP levels. Some studies have reported aspirin reduced CRP levels, but other studies did not. This study was designed to assess the effect of low-dose aspirin on CRP levels in controlled hypertensive patients who had low inflammatory burden. Two hundred twenty-five patients with controlled hypertension were randomly divided into two groups; aspirin group (n = 122, 100 mg of aspirin) and the control group (n = 134). Patients with a CRP level >1 mg/dL (10 mg/L) were excluded because these high levels suggest infection. C-reactive protein level and lipid profiles were measured before therapy and 3 months after therapy. There were no differences in baseline clinical characteristics between the two groups. Low-dose aspirin showed no significant influence on CRP levels over 3 months (from 0.10 ± 0.0099 to 0.12 ± 0.0097 mg/dL, p = 0.12). Statin therapy did not influence CRP levels. Aspirin-resistance also had no influence on CRP levels. We conclude that low-dose aspirin has no significant effect on decreasing CRP levels in the patients with controlled hypertension which had low inflammatory burden. The anti-inflammatory mechanism may not play an important role in the cardioprotective effect of aspirin in the population with low inflammatory burden such as controlled hypertensive patients.