Objective To explore the relationship between thrombocytosis and all-cause in-hospital mortality in patients with chronic obstructive pulmonary disease (COPD) and low-risk pulmonary embolism (PE). Methods In a multicenter retrospective study on clinical characteristics, COPD patients with proven acute PE between October 2005 and February 2017 were enrolled. The patients in risk classes III-V on the basis of the PESI score were excluded. The patients with COPD and low-risk PE were divided into two groups of those with thrombocytosis and without thrombocytosis after extracting platelet count on admission. The clinical characteristics and prognosis of the two groups were compared. Multivariate logistic regression was performed to reveal an association between thrombocytosis and all-cause in-hospital mortality after confounding variables were adjusted. Results A total of 874 consecutive patients with COPD and PE at low risk were enrolled in which 191 (21.9%) with thrombocytosis. Compared with those without thrombocytosis, the thrombocytopenic group had significantly lower body mass index [(20.9±3.3) kg/m2 vs. (25.1±3.8) kg/m2, P=0.01], lower levels of forced expiratory volume in one second (FEV1) [(0.9±0.4) L vs. (1.3±0.3) L, P=0.001] and lower partial pressure of oxygen in the arterial blood (PaO2) [(7.8±1.2) kPa vs. (9.7±2.3) kPa, P=0.003]. The COPD patients with thrombocytosis had a higher proportion of cardiovascular complications as well as higher level of systolic pulmonary arterial pressure (sPAP) [(46.5±20.6) mm Hg vs. (34.1±12.6) mm Hg, P=0.001]. Multivariate logistic regression analysis after adjustment for confounders revealed that thrombocytosis was associated with all-cause mortality in hospitalized patients with COPD and low-risk PE (adjusted OR=1.53, 95%CI 1.03–2.29), and oral antiplatelet treatment was a protective factor (adjusted OR=0.71, 95%CI 0.31–0.84). Conclusions Thrombocytosis is an independent risk factor for all-cause in-hospital mortality in COPD patients with PE at low risk. Antiplatelet therapy may play a protective role in the high-risk cohort.