Is the Oral Microbiome Associated with Blood Pressure in Older Women? Abstract Introduction A possible role of the oral microbiome, specifically oral nitrate reducing flora, in blood pressure (BP) homeostasis, if proven etiologic in nature, could lead to novel mechanism-based therapy to improve hypertension prevention and control. Aim This cross-sectional study characterized and compared the oral microbiome between four study groups based on BP status among 446 postmenopausal women aged 53–82 years. Methods Three study groups were not taking hypertension medication and were separated based on BP, as follows: normal BP (systolic < 120 and diastolic < 80; N = 179), elevated BP/Stage I hypertension (systolic 120–139 or diastolic 80–90; N = 106), Stage II hypertension (systolic > 140 or diastolic > 90; N = 42). The forth group consisted of anyone taking hypertension medications, regardless of BP (N = 119). Subgingival microbiome composition was determined using 16S rRNA sequencing with the Illumina MiSeq platform. Kruskal–Wallis tests were used to compare species-level relative abundance of bacterial operational taxonomic units across the four groups. Results Sixty-five bacterial species demonstrated significant differences in relative abundance in women with elevated BP or using hypertension medication as compared to those with normal BP. After correction for multiple testing, two species, Prevotella oral (species 317) and Streptococcus oralis, remained significant and were lower in abundance among women taking antihypertension medications compared to those with normal BP (corrected P < 0.05). Conclusions These data provide novel description of oral subgingival bacteria grouped according to BP status. Additional larger studies including functional analysis and prospective designs will help further assess the potential role of the oral microbiome in BP regulation and hypertension.