Background: Pleural effusion is observed in a subset of patients with acute pulmonary embolism (APE) and may be linked to clinical outcome, but findings from previous studies have been inconsistent. This study aimed to investigate the prevalence and clinical significance of pleural effusion in Chinese patients with APE. Methods: Clinical data from hospitalized patients with APE were retrospectively collected and the prevalence of pleural effusion was determined. The relationship between the presence of pleural effusion and clinical outcome of APE was analyzed by Cox proportional hazards regression and Kaplan-Meier survival analysis. Results: The study enrolled 635 patients with APE. The prevalence of pleural effusion was 57.01% (362/635). Patients with pleural effusion had significantly higher in-hospital mortality (9.9% vs. 4.8%, P<0.05) and longer length of hospital stay (LOS) (19.99 vs. 15.31 days, P<0.05) than whose without pleural effusion. However, pleural effusion was not an independent risk factor for in-hospital mortality in patients with APE by multivariate Cox proportional hazards regression analysis [hazard ratio (HR) =1.70, 95% confidence interval (CI): 0.73-3.92, P=0.216] and Kaplan-Meier survival analysis (P=0.174). Conclusions: Pleural effusion is a frequent occurrence in patients with APE and therefore merits greater attention from clinicians; however, it is not an independent risk factor for in-hospital mortality.