Background Effective thromboprophylaxis is critical to reducing mortality and improving clinical outcomes in COVID-19 patients. Despite guidelines recommending prophylactic anticoagulation, particularly for those in intensive care, real-world adherence and optimal venous thromboembolism (VTE) prevention strategies remain challenging, particularly in populations with complex comorbidities. Methods A prospective study was conducted on patients hospitalized with moderate, severe, and critical COVID-19 in six Chinese hospitals during the Omicron pandemic (December 2022-January 2023). The dose and duration of low-molecular-weight heparin (LMWH) were recorded. VTE, all-cause mortality and major bleeding events during hospitalization and 90-days follow-up were analyzed as endpoints. Results Among 4,236 COVID-19 patients, 1575 (37.09%) received LMWH prophylaxis, with 592 (37.6%) receiving reduced dosage (< 4000IU/24 h). The multivariable logistic regression model revealed that age >= 65, elevated D-dimer levels, severely ill at admission and concomitant use of antiviral drugs or corticosteroids were the main factors influencing the initiation of LMWH thromboprophylaxis in hospitalized COVID-19 patients. Patients who were critically ill at admission were more likely to receive reduced doses of LMWH. The duration of thromboprophylaxis over 7 days was associated with reduced estimated glomerular filtration rate (eGFR) and concomitant use of antiviral drugs or corticosteroid, whereas shorter durations were observed in patients with platelet less than 100*109/L and anemia. Conclusion Real-world thromboprophylaxis in hospitalized COVID-19 patients vary widely, with a significant proportion receiving lower-than-conventional doses of LMWH. There is a need for individualized thromboprophylaxis strategies that consider patient-specific factors such as disease severity, renal function, low platelet and anemia to optimize outcomes.