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Background: External ventricular drain (EVD)-related infection (ERI) is a common complication in cranial neurosurgery practice with high mortality. The risk factors associated with ERI are not well studied in low- and middle-income countries (LMIC) like India. Identifying the risk variables is a necessity to design robust evidence-based care bundles for ERI prevention. Materials and methods: This is a single-center prospective cohort study. Patients with and without ERI during the 2-year study period were analyzed along with literature review to identify the risk variables associated with ERI. The Institute for Healthcare Improvement (IHI) comprehensive flowchart was used to develop the concept care bundle for ERI prevention. Results: A total of 211 EVD were inserted during the study period. 15 ERI (7.1%) were identified based on IDSA criteria, with an average infection rate of 11.12 per 1000 EVD days. Gram negative bacteria (GNB) were the predominant pathogen (12/15, 80%), with Klebsiella pneumoniae (6/15, 40%) being the most common bacteria isolated. In multivariate analysis, the risk variables associated with ERI were use of broad spectrum pre-surgical antimicrobial prophylaxis for long duration, choice of posterior craniometric points for EVD insertion, EVD duration >7 days, EVD leak and surveillance cerebrospinal fluid (CSF) sampling at periodic intervals. Based on the risk variables identified in this study and literature review, a consensus decision on the care elements for the insertion and maintenance phases was chosen for the concept care bundle for ERI prevention. Conclusion: An evidence-based concept care bundle for ERI prevention is proposed for further multicentric evaluation and validation. [ABSTRACT FROM AUTHOR]