OBJECTIVES: To determine efficacy of continuous heparin infusion vs placebo on maintenance of peripherally inserted central catheter line among neonates admitted at the NICU. METHODS: This is a meta-analysis of randomized controlled trials reported in accordance with PRISMA checklist. Cochrane Risk-of-bias tool was used in assessment of reporting biases. Pooled risk ratios were estimated using random- or fixed-effects model. RESULTS: Of 4519 studies identified, 4 studies were included, and all have low risk of bias. Meta-analysis showed that continuous heparin infusion on PICCs had significantly higher duration of catheter patency compared to the placebo group (MD=2.22, 95%CI=1.03-3.14, pvalue<0.00001). Heparin group also had decreased risk of occlusion (RR=0.47, 95%CI=0.94, pvalues=0.03) compared to control. The risk for other adverse events such as thrombosis, infection, IVH progression, and mortality was comparable between the two groups. CONCLUSION: Continuous heparin infusion in PICC fluids can prolong duration of catheter patency by 2.2 days and reduce risk of catheter-related occlusion by 50%, without having significant effect on incidence of other adverse events. RECOMMENDATIONS Continuous heparin infusion on PICC fluids should be part of maintenance and care policy at the NICU, but precautions should be followed to prevent adverse outcomes. Systematic review of intermittent heparin flushing can be a window of opportunity.