Objective To study the effect of intensive intervention measures based on compliance monitoring on prevention and control of Acinetobacter baumannii (AB) infection in intensive care unit (ICU). Methods Inpatients and health care workers (HCWs) in the general ICU of a tertiary first-class hospital from January 2019 to December 2020 were selected as the research objects. Baseline survey was conducted from January to December 2019 (before intervention) to investigate the basic condition of AB infection and colonization in patients. Intensive prevention and control strategies for multidrug-resistant organism (MDRO) were implemented from January to December 2020 (after intervention). A multi-department collaborative management team was set up to monitor compliance to prevention and control measures. Compliance to prevention and control measures, antimicrobial use, incidence of healthcare-associated infection (HAI), and changes of drug resistance of AB were compared. Results After the intervention, HCWs' compliance to prevention and control measures improved, implementation rate of single room isolation increased from 15.52% before intervention to 27.71% after intervention, HCWs' compliance rate to hand hygiene, wearing gloves and wearing isolation gown as well as the clearance rate of fluorescent markers on the environmental surface all improved in varying degrees (all P < 0.001). After intervention, the utilization rate of antimicrobial agents was lower than that before intervention (74.24% vs 80.06%, P=0.002), DDDs of antimicrobial use density was lower than those before intervention. After intervention, HAI rate, constituent ratio of AB HAI, and incidence of carbapenem-resistant AB (CRAB) HAI in patients decreased, difference was statistically significant (all P < 0.05). The main pathogens isolated from patients before and after intervention were both AB, constituent ratio of isolated AB after intervention was lower than that before intervention (21.24% vs 30.77%, P < 0.05). Antimicrobial resistance rates of AB to imipenem and meropenem decreased from 76.32% and 74.34% before intervention to 60.58% and 58.39% after intervention respectively, resistance rate to tegacyclin decreased from 10.53% before intervention to 1.46% after intervention (both P < 0.05). Conclusion Intensive prevention and control measures based on compliance monitoring has a good effect on reducing HAI and resistance of AB in ICU.