Introduction An individualised thromboprophylaxis was implemented in critically ill patients suffering from coronavirus disease 2019 (COVID-19) pneumonia to reduce mortality and improve clinical outcome. The aim of this study was to evaluate the effect of this intervention on clinical outcome. Methods In this mono-centric, controlled, before-after study, all consecutive adult patients with confirmed COVID-19 pneumonia admitted to ICU from March 13th to April 20th 2020 were included. A thromboprophylaxis protocol, including augmented LMWH dosing, individually tailored with anti-Xa measurements and twice-weekly ultrasonography screening for DVT, was implemented on March 31th 2020. Primary endpoint is one-month mortality. Secondary outcomes include two-week and three-week mortality, the incidence of VTE, acute kidney injury and continuous renal replacement therapy (CRRT). Multiple regression modelling was used to correct for differences between the two groups. Results 46 patients were included in the before group, 26 patients in the after group. One month mortality decreased from 39.13% to 3.85% (p < 0.001). After correction for confounding variables, one-month mortality was significantly higher in the before group (p = 0.02, OR 8.86 (1.46, 53.75)). The cumulative incidence of VTE and CRRT was respectively 41% and 30.4% in the before group and dropped to 15% (p = 0.03) and 3.8% (p = 0.01), respectively. After correction for confounding variables, risk of VTE (p = 0.03, 6.01 (1.13, 32.12)) and CRRT (p = 0.02, OR 19.21 (1.44, 255.86)) remained significantly higher in the before group. Conclusion Mortality, cumulative risk of VTE and need for CRRT may be significantly reduced in COVID-19 patients by implementation of a more aggressive thromboprophylaxis protocol. Future research should focus on confirmation of these results in a randomized design and on uncovering the mechanisms underlying these observations. Registration number NCT04394000 .