AbstractPatients undergoing knee joint replacement (KJR) are at high risk of postoperative venous thromboembolism (VTE), but data on the time trends of VTE rate in this population are sparse. In this analysis of the German nationwide inpatient sample, we included all hospitalizations for elective primary KJR in Germany 2005–2016. Overall, 1,804,496 hospitalized patients with elective primary KJR (65.1% women, 70.0 years [IQR 63.0–76.0]) were included in the analysis. During hospitalization, VTE was documented in 23,297 (1.3%) patients. Total numbers of primary KJR increased from 129,832 in 2005 to 167,881 in 2016 (β-(slope)-estimate 1,978 [95% CI 1,951 to 2,004], P < 0.001). In-hospital VTE decreased from 2,429 (1.9% of all hospitalizations for KJR) to 1,548 (0.9%) cases (β-estimate − 0.77 [95% CI − 0.81 to − 0.72], P < 0.001), and in-hospital death rate from 0.14% (184 deaths) to 0.09% (146 deaths) (β-estimate − 0.44 deaths per year [95% CI − 0.59 to − 0.30], P < 0.001). Infections during hospitalization were associated with a higher VTE risk. VTE events were independently associated with in-hospital death (OR 20.86 [95% CI 18.78–23.15], P < 0.001). Annual number of KJR performed in Germany increased by almost 30% between 2005 and 2016. In parallel, in-hospital VTE rates decreased from 1.9 to 0.9%. Perioperative infections were associated with higher risk for VTE. Patients who developed VTE had a 21-fold increased risk of in-hospital death.