Objective: To investigate the correlation of serum lipoprotein-associated phospholipase (Lp-PLA2), red blood cell distribution width (RDW) levels with early neurological deterioration (END) in elderly patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods: A total of 217 elderly patients with AIS admitted to Liaoyang Central Hospital from January 2019 to December 2020 were selected as the research subjects. Their clinical data, including general data, laboratory indicators, and National Institutes of Health Stroke Scale (NIHSS) score, were retrospectively analyzed. The patients were divided into an END group (n=52) and a non-END group (n=165) according to whether END occurred. The relationship between related indexes and END was analyzed by univariate logistic regression model, and the evaluation value of Lp-PLA2 and RDW for END was analyzed by receiver operating characteristic (ROC) curve. Results: END occurred in 52 (23.96%) of 217 elderly AIS patients. Compared with the non-END group, the END group had longer ONT and thrombolysis time, higher NIHSS score at admission, higher serum Lp-PLA2, and RDW levels (t=3.318, 4.957, 4.264, 15.196, 4.191, all P<0.05). Lp-PLA2 and RDW were positively correlated with NIHSS score (r=0.389, 0.311, all P<0.05). Logistic regression analysis showed that ONT (OR =1.093), NIHSS score at admission (OR =1.135), Lp-PLA2 (OR =1.629), and RDW (OR =1.344) were independent influencing factors of END (all P<0.05). ROC curve analysis showed that the area under the curve (AUC) of Lp-PLA2 and RDW for END was 0.907 and 0.666, the sensitivity was 84.62% and 50.00%, and the specificity was 89.09% and 83.03%. Conclusion: Lp-PLA2 and RDW are related to the occurrence of END in elderly AIS patients after intravenous thrombolysis. Higher levels of Lp-PLA2 and RDW suggest that patients have a high risk of END.