Abstract Objective Coronary slow flow (CSF) is characterized by delayed opacification of distal epicardial coronary arteries without significant coronary stenosis. In addition, The changes of lipoprotein-associated phospholipase A2 (Lp-PLA₂) as a significant predictive factor for CSF remain controversial. The study aims to investigate the association between plasma Lp-PLA₂ and CSF. Methods In this retrospective study, 170 consecutive patients who underwent coronary angiography were enrolled in Beijing Anzhen Hospital from January 2017 to September 2019, and were divided into CSF group and normal control groups. According to coronary blood flow rate measured by the thrombolysis in myocardial infarction frame count (TFC) method, CSF was defined as TFC > 27. Serum Lp-PLA₂ levels were measured in an enzyme-linked immunosorbent assay. Results Lp-PLA₂ levels were higher in the CSF group than in the control group (288.6 ± 50.3 versus 141.9 ± 49.7, P < 0.001) and were significantly correlated with the mean coronary artery thrombolysis in myocardial infarction (TIMI) frame count (r = 0.790, P<0.001). Logistic regression analysis showed that high Lp-PLA₂ was independently associated with CSF after adjustment for conventional risk factors (OR = 1.040, CI = 1.022–1.059, P<0.001). Male sex (OR = 2.192, CI = 1.161–4.140, P = 0.016) and hypertension (OR = 1.965, CI = 1.034–3.736, P = 0.039) were also CSF risk factors. Receiver-operating characteristic curve (ROC) analysis showed that Lp-PLA₂ levels can predict CSF severity; the predictive power was higher than the other risk factors. Conclusion Our study demonstrated that patients with CSF had higher circulating levels of Lp-PLA₂ than normal controls. After adjustment for potential confounders, increased Lp-PLA₂ was independently associated with presence of CSF.