Background: Interventional studies on the effect of alcohol-based hand rub on ventilator-associated pneumonia (VAP) among neurosurgical patients are scarce. Aim: To observe the effect of alcohol-based hand rub on tracheobronchial colonization and VAP after elective neurosurgical procedures. Materials and Methods: An interventional study using a “before-after” design in a tertiary care center in Kerala. Two 9-month study periods were compared; between these periods, an infection control protocol incorporating an alcohol-based hand rub was implemented for a period of 3 months and continued thereafter. Consecutive patients who required mechanical ventilation after neurosurgery between January and September 2006 and 2007, respectively, were included. Outcome measures included VAP rate, tracheobronchial colonization rate, profile of microorganisms and patient survival. Results: A total of 352 patients were on mechanical ventilator for a varying period of 1-125 days. The patients in the control and intervention groups were similar with regard to sex, age and type of neurosurgery. Tracheobronchial colonization was seen in 86 (48.6%) of 177 in the control group and 73 (41.7%) of 175 among the intervention group (P = 0.195). The VAP rates in the control and intervention groups were 14.03 and 6.48 per 1000 ventilator days (P = 0.08). The predominant organisms causing VAP and tracheobronchial colonization were Klebsiella and Pseudomonas aeruginosa, respectively, in both groups. Patient survival rates were 87.6% (control) and 92% (intervention). Conclusion: Clinical results indicated a better outcome, showing a reduction in tracheobronchial colonization rate and VAP rate, although this was not statistically significant.