Whether intermittent pneumatic compression (IPC) is a more effective form of thromboprophylaxis than anticoagulants in individuals undergoing neurosurgery remains controversial. Relevant studies are sparse and inconsistent. Therefore, direct comparisons are difficult to perform and impractical. Hence, we summarized and compared the efficacy and safety of IPC and anticoagulants for the prevention of venous thromboembolism (VTE) in adults undergoing cranial or spinal procedures. Several electronic databases were searched for randomized controlled trials on the use of IPC and anticoagulants for thromboembolism prevention in neurosurgical patients, from inception to August 6, 2019. Studies reporting the selected endpoints were included in direct and Bayesian network meta-analyses to estimate the relative effects of the interventions. Overall, our analysis included 18 trials comprising 2474 patients. Both IPC (RR, 0.41; 95% CrI, 0.26-0.60) and chemical prophylaxis (RR, 0.48; 95% CrI, 0.28-0.68) were found to be more efficacious than the placebo in reducing the risk of deep vein thrombosis (DVT). In addition, our analysis also demonstrated that both IPC (RR, 0.10; 95% CrI, 0.01-0.60) and chemical prophylaxis (RR, 0.31; 95% CrI, 0.05-1.00) reduced the risk of pulmonary embolism (PE) significantly more than the placebo. Based on the available evidence of moderate-to-good quality, IPC is equivalent to anticoagulants for thromboprophylaxis in terms of efficacy. Evidence to support or negate the use of pharmacological prophylaxis in terms of safety is lacking. The results of ongoing and future large randomized clinical trials are needed.