Although basic medical studies have shown that lysophosphatidic acid (LPA) has an important relationship to activated blood platelets, we know little about this from clinical experience. This pilot study examined plasma LPA levels in patients with a risk of thrombotic events and evaluated the effects of aspirin on plasma LPA levels. In this basically cross-sectional study, we recruited 1352 patients with either hypertension or hyperlipidemia and 670 controls without any risk factors. Patients with risk factors had significantly higher plasma LPA levels than controls, the mean of LPA = 3.12 ± 2.24 vs. 2.57 ± 1.96 μmol/l, P < 0.001. The patients who had been taking aspirin had relatively lower plasma LPA levels compared with those who did not take aspirin, χ2 = 43.8, odds ratio (OR) [95% confidence interval (CI)] = 2.76 (2.03–3.75). For the hypertension group, χ2 = 23.1, OR (95% CI) = 3.44 (2.03–5.82), P < 0.001; for the hyperlipidemia group, χ2 = 22.9, OR (95% CI) = 2.53 (1.72–3.74), P < 0.001. Patients with a risk factor had higher plasma LPA levels compared with controls. Administration of aspirin may decrease elevated plasma LPA levels. This pilot clinical observation indicates that plasma LPA is worth to be studied further.