Background: CSF infection is a significant complication of ventriculoperitoneal (VP) shunts and results in prolonged hospital stay, developmental delay and decreased quality of life. To decrease the high rates of neonatal VP shunt infections, an updated clinical guideline that included the use of antibiotic-impregnated shunts and a revised peri-operative antibiotic protocol was introduced in our neonatal unit. In this study, we evaluated the efficacy of these new guidelines in reducing the CSF shunt infection rates. Methods: A retrospective cohort study of neonates (≤28 days) who had VP shunt insertions in our unit. Results: 24 neonates in the first epoch received plain silastic shunt catheters (Feb 2002–April 2007), and 23 in the second epoch (August 2007–July 2015) received AIS catheters and a revised perioperative antibiotic protocol. Patient demographics were similar between both cohorts. Shunt related CSF infections were reduced in epoch 2 (2/23, 8.7%) compared to epoch 1 (5/24, 20.8%), but the results were not statistically significant (OR 0.36 (0.063–2.090); p = 0.256). Amongst neonates that needed VP shunt revision due to any cause, the median time interval between insertion to revision was significantly later in epoch 2 (epoch 1, 48 days (3–99); epoch 2, 148 days (20–396); p = 0.013). Conclusions: AIS catheters and a 48-hour perioperative antibiotic regimen may be beneficial in neonatal hydrocephalus. Adequately powered RCTs in the neonatal population are needed to confirm these findings.