Purpose Studies on the epidemiology of bloodstream infection (BSI) and antimicrobial resistance (AMR) are limited in Vietnam. Thus, the present study aimed to elucidate the epidemiology of BSI and AMR of BSI-causing bacteria in Vietnam. Methods Data regarding blood cultures from 2014 to 2021 were collected and analyzed using the chi-square test, Cochran–Armitage test, and binomial logistic regression model. Results Overall, 2405 (14.15%) blood cultures were positive during the study period. In total, 55.76% of BSIs occurred in patients aged ≥60 years. The male-to-female ratio of patients with BSI was 1.87:1. Escherichia coli (26.11%), Staphylococcus aureus (15.79%), Klebsiella pneumoniae (10.44%), Acinetobacter baumannii (4.70%), and Pseudomonas aeruginosa (3.45%) were the leading bacterial species causing BSI. The AMR rate of these bacteria isolated in the intensive care unit (ICU) was significantly higher compared with that of those in other wards. E. coli was the least resistant to carbapenems (2.39%–4.14%), amikacin (3.85%), and colistin (11.54%) and most resistant to penicillins (>80.0%). S. aureus was the least resistant to glycopeptides (0%–3.38%), quinupristin-dalfopristin (0.59%), and linezolid (1.02%) and most resistant to clindamycin (71.57%). K. pneumoniae was the least resistant to ertapenem (8.86%), amikacin (9.39%), and colistin (15.38%) and most resistant to aztreonam (83.33%). A. baumannii was the least resistant to amikacin (16.67%) and colistin (16.67%) and highly resistant to other antibiotics (≥50.0%). P. aeruginosa was the least resistant to colistin (16.33%) and piperacillin (28.17%) and highly resistant to other antibiotics (≥50.0%). Notably, the multidrug resistance rate of E. coli (76.41%) was the highest among common pathogens, followed by A. baumannii (71.57%), P. aeruginosa (64.56%), S. aureus (56.99%), and K. pneumoniae (43.72%). Conclusion The AMR rate of BSI-causing bacteria, particularly strains isolated from ICU, was alarmingly high. There is a need for new antibiotics, therapeutic strategies, as well as prevention and control to combat BSI and AMR.