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Abstract Background To determine the efficacy and safety of heparin (unfractionated heparin (UFH) or low-molecular-weight-heparin (LMWH)) and fondaparinux in improving the survival of patients with cancer. Methods We conducted in January 2007 a comprehensive search for relevant randomized clinical trials (RCTs). We used a standardized form to extract in duplicate data on methodological quality, participants, interventions and outcomes of interest including all cause mortality, thromboembolic events, and bleeding events. We assessed the methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology Results Of 3986 identified citations, we included 5 RCTs, none of which evaluated fondaparinux. The quality of evidence was moderate for survival, low for major and minor bleeding, and very low for DVT. Heparin therapy was associated with a statistically and clinically significant survival benefit (hazard ratio (HR) = 0.77; 95%CI = 0.65–0.91). In subgroup analyses, patients with limited small cell lung cancer experienced a clear survival benefit (HR = 0.56; 95%CI = 0.38–0.83). The survival benefit was not statistically significant for either patients with extensive small cell lung cancer (HR = 0.80; 95%CI = 0.60–1.06) or patients with advanced cancer (HR = 0.84; 95%CI = 0.68–1.03). The increased risk of bleeding with heparin was not statistically significant (relative risk (RR) = 1.78; 95%CI = 0.73–4.38). Conclusion This review suggests a survival benefit of heparin in cancer patients in general, and in patients with limited small cell lung cancer in particular.