Abstract: OBJECTIVE To observe the influence of comprehensive intervention measures on incidence of multidrug-resistant organisms (MDROs) infections in neonates. METHODS By means of retrospective survey, the data were collected from the patients who were hospitalized neonatal wards from Jan 1, 2014 to Jun 30, 2014, then the comprehensive intervention was conducted from Jul 1, 2014 to Jun 30, 2015, and the incidence of MDROs infections and the isolation rates were observed and compared before and after the intervention. RESULTS The separation rate of MDROs infections increased from 68.66% to 97.80% after the comprehensive intervention (P＜0.05); the hand hygiene compliance rate increased from 70.25% to 89.50% (P＜0.05); the incidence of MDROs infections dropped from 4.60% to 3.38%(P＜0.05); the isolation rate decreased from 33.50% to 22.03% (P＜0.05). CONCLUSION It is an effective way to take the comprehensive interventions such as issuing the medical advice of contact and isolation, conducting supervision and assessment, and improving the hand hygiene compliance rate so as to reduce the incidence of MDROs infections.