To address whether periodontal disease indexes are associated with urinary albumin-to-creatinine ratio (UACR) in conditions of high and low systemic inflammation as reflected by levels of high-sensitivity C-reactive protein (hs-CRP) in untreated hypertensive patients, we studied 242 hypertensive patients 51 ± 9 years old (24-hour systolic/diastolic blood pressure [BP] 132 ± 10/83 ± 8 mm Hg) with varying severity of periodontal disease evaluated by 3 periodontal disease indexes (PDIs) (i.e., mean clinical loss of attachment, maximum probe depth, and gingival bleeding index). Patients underwent BP measurements, echocardiography, and periodontal examination, and from fasting blood samples we assessed metabolic profile and hs-CRP. From 2 nonconsecutive overnight spot urine samples we evaluated UACR. With respect to median hs-CRP and UACR levels (1.67 mg/L and 10 mg/g, respectively), the total population was divided into patients with low-UACR/low-hs-CRP (n = 65), low-UACR/high-hs-CRP (n = 63), high-UACR/low-hs-CRP (n = 51), and high-UACR/high-hs-CRP (n = 63). PDIs differed among the 4 groups, and those with high UACR had significantly higher 24-hour systolic BP compared to those with low UACR. UACR was determined by all periodontal disease indexes, hs-CRP, and the interaction of each periodontal disease index with hs-CRP. In addition, mean clinical loss of attachment was the strongest determinant of the high-UACR/high-hs-CRP pattern among all studied periodontal disease indexes. In conclusion, in untreated middle-aged hypertensive patients, periodontal disease indexes and hs-CRP have a synergistic effect on UACR levels independently of the underlying hemodynamic load.