Introduction: Venous thromboembolism prevention during critical illness is a widely-used quality metric. The purpose of this systematic review was to evaluate the the efficacy and safety of heparin thromboprophylaxis in medical-surgical patients in the intensive care unit (ICU). Hypothesis: Heparin will be effective at preventing DVT and PE in the ICU, as in other settings. LMWH will be more effective than UFH at preventing PE. Methods: We searched EMBASE, MEDLINE, the Cochrane Controlled Trials Register, clinicaltrials.gov and personal files to May 2012. We included randomized trials in adult medical-surgical ICU patients comparing any heparin thromboprophylaxis to another approach, evaluating deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding or mortality. In triplicate we abstracted trial characteristics, outcomes and risk of bias. Results: Seven trials involved 7226 patients. Any heparin thromboprophylaxis compared to placebo reduced rates of DVT (pooled risk ratio [RR] 0.51; 95% CI, 0.41, 0.63; P<0.0001; I2=77%) and PE (RR 0.52; 95% CI 0.28, 0.97; P=0.04; I2=0%), but not symptomatic DVT (RR 0.86; 95% CI 0.59, 1.25; P=0.43). Major bleeding (RR 0.82; 95% CI 0.56, 1.21; P=0.32; I2=50%) and mortality (RR 0.89; 95% CI 0.78, 1.02; P=0.09, I2=0%) rates were similar. Compared to unfractionated heparin (UFH), low molecular weight heparin (LMWH) reduced rates of PE (RR 0.62; 95% CI 0.39, 1.00; P=0.05; I2=53%) and symptomatic PE (RR 0.58; 95% CI 0.34, 0.97; P=0.04) but not DVT (RR 0.90; 95% CI 0.74, 1.08; P=0.26; I2=0%), symptomatic DVT (RR 0.87; 95% CI 0.60, 1.25; P=0.44; I2=0%), major bleeding (RR 0.97; 95% CI 0.75, 1.26; P=0.83; I2=0%), or mortality (RR 0.93; 95% CI 0.82, 1.04; P=0.20; I2=31%). Some inferences are limited by heterogeneity and imprecision. Conclusions: In medical-surgical ICU patients, heparin thromboprophylaxis significantly decreases DVT and PE risk, and LMWH significantly decreases PE risk compared to UFH. Anticoagulant thromboprophylaxis does not affect bleeding or mortality rates.