The irrational use of antibiotics is one of the factors in the emergence of Multidrug Resistance (MDR) bacterial infections, which is estimated to continue to increase patient’s mortality until 2050. This study aims to analyse the factors that influence the development of bacterial resistance in bloodstream infections in Critical care settings at a tertiary hospital in Indonesia. This study is an observational retrospective study with Case-control research method. This research uses the electronic medical record (EMR) data of the inpatients in the Intensive Care Unit and High Care Unit at Dr. Soetomo Academic Hospital, Surabaya, Indonesia, from July 2023 to June 2024. Total of 97 patients with bloodstream infection by MDR bacteria detected were recruited as the sample group. Patients with bloodstream infection but no resistance detected during the hospitalization period were recruited as the control group with 1:1 proportion. There were 172 antibiotic prescriptions in the sample group and 183 in the control group. It was found that the factors that influence the development of resistance were prophylactic antibiotic used in non-surgical (adjusted OR = 9.187; CI 95% = 1.9-44.37; p = 0.006), the use of endotracheal tube (adjusted OR = 2.30; CI 95% = 1.37-3.86; p = 0,002) and immune suppression medication (adjusted OR = 2.709; CI 95% = 1.3-5.65; p = 0.008). This study indicates that in Critical care population of Dr. Soetomo General Academic Hospital, the use of non-surgical prophylaxis antibiotics, endotracheal tube devices, and immune suppression caused by medications were significant factors that increase bacterial resistance in bloodstream infection.