Symptomatic venous thromboembolism (VTE) occurs in 15% of patients with advanced malignancy. Primary thromboprophylaxis using low-molecular-weight heparin (LMWH) is supported by Level 1A evidence but is under-utilized in the palliative setting. A systematic search was performed of Medline, Cochrane Library, EMBASE, AMED, and Web of Science for papers published between 1960 and January 2010 using search terms: ‘palliative’, ‘thromboprophylaxis’, ‘thromboembolism’, ‘heparin’, and ‘advanced cancer’. Forty-two citations were obtained, of which 34 were excluded as they dealt with treatment of VTE, novel anticoagulants, or LMWH as a cancer treatment. Eight original articles were reviewed independently by two authors. Data was extracted according to a predetermined questionnaire. Studies examined practice in specialist palliative care (SPC) units, and attitudes held by a total of 32 physicians and 198 patients. Patients find LMWH acceptable, particularly patients who experienced a sudden decline in performance status. Reluctance to prescribe LMWH is based on physicians’ concerns regarding negative impact on quality of life, and lack of evidence specific to the palliative care setting. In conclusion, LMWH prophylaxis should be implemented in patients with a previously good performance status who have a transiently increased risk of VTE and no contraindications. Further research is required using outcome measures specific to palliative care.