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Background: Thromboembolism (TE) is a leading cause of death in cancer patients. Primary thromboprophylaxis (PTP) in ambulatory cancer patients receiving chemotherapy has been debated and considered to potentially improve survival by reducing TE occurrence. Objective: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in ambulatory lung cancer (LC) patients on chemotherapy to determine the benefit and risk of PTP with low-molecular-weight heparins (LMWHs). Method: A literature search using MEDLINE and EMBASE databases was performed through June 2016. RCTs with venous thromboembolism (VTE) reduction as primary or secondary endpoints were included. Mantel-Haenszel method was used to estimate the pooled event risk ratio as well as pooled absolute risk difference with 95% confidence interval (CI). Result: A total of 4315 LC patients from six studies were available for analysis. PTP lasted for 4 to 6 months. The venous thromboembolism (VTE) incidence was 4.0% and 7.9% in LMWH and control groups, respectively (risk ratio, 0.510 (95% CI, 0.397-0.654, P < 0.001). The absolute risk difference in VTE was -0.039 (95% CI, -0.053 to -0.025, P < 0.001), with an estimated number needed to treat (NNT) of 25 to prevent one VT Eevent. The pooled risk ratio for major bleeding was 1.468 (95% CI, 0.785-2.746, P = 0.229). The pooled risk ratio for overall survival was statistically nonsignificant at 1.020 (95% CI, 0.938-1.109, P = 0.648). Conclusion: Routine PTP for ambulatory LC patients receiving chemotherapy is not recommended and further studies are necessary to define a subset of ambulatory LC patients receiving chemotherapy who may benefit from PTP. [ABSTRACT FROM AUTHOR]