Background: Pharmaceutical inhibition of host response pathways may be an adjunctive or alternative strategy for treating periodontal diseases. In addition to inhibition of prostaglandin synthesis, aspirin is known to modify the action of cyclooxygenase, changing its activity to a lipoxygenase and leading to formation of lipoxins which have a proresolving effect. This study evaluated the periodontal attachment level of subjects on long-term low dose aspirin therapy. Methods: Oral hygiene index simplified, clinical attachment loss and bleeding index were recorded for 162 subjects who were on long-term (>6 months) low dose (75 mg and 150 mg) aspirin therapy (study group) and 146 subjects not taking the drug (control group). Results: Mean clinical attachment loss was 2.38 ± 0.49 mm in the control group and 2.01 ± 0.69 mm in the study group. The difference was statistically significant at p < 0.001. Correlation analysis suggested that there was a negative correlation between clinical attachment loss and duration of aspirin intake but the clinical attachment loss was not significantly different in the two dosage groups. Conclusions: The results of this study suggest that low dose aspirin may reduce the risk of periodontal attachment loss. This hypothesis needs to be tested by larger sample sized prospective cohort studies.