Hospitalized cancer patients are at high risk of venous thromboembolism (VTE). Despite current recommendations in clinical guidelines, thromboprophylaxis with low molecular weight heparin (LMWH) is underused. We performed an observational prospective study to analyse factors influencing prophylaxis use, VTE events and mortality in cancer-hospitalized patients. 1072 consecutive adult cancer patients were included in an University Hospital from April 2014 to February 2017, and followed-up for 30 days after discharge. The rate of LMWH prophylaxis was 67.6% (95% confidence interval CI 64.7% to 70.4%), with a 2.8% rate of VTE events (95% CI 1.9% to 3.9%) and 3.5% rate of major bleeding events (95% CI 2.5% to 4.8%). 80% of VTE events occurred despite appropriate thromboprophylaxis. Overall, 30-day mortality rate was 13.2% (95% CI 11.2% to 15.3%). Active chemotherapy treatment, hospital stay ≥ 4 days, and metastatic disease were associated with a higher use of LMWH. On the contrary, patients with hematologic malignancies, anemia or thrombocytopenia were less prone to receive thromboprophylaxis. The main reasons for not prescribing LMWH prophylaxis were thrombocytopenia (23.9%) and active/recent bleeding (21.8%). The PRETEMED score, used for VTE risk stratification, correlated with 30-day mortality. There is room for improvement in thromboprophylaxis use among hospitalized-cancer patients, especially among those with hematologic malignancies. A relevant number of VTE events occurred despite prophylaxis with LMWH. Therefore, identification of risk factors for thromboprophylaxis failure is needed.