Nosocomial bloodstream infections (NBSIs) are adverse complications of hospitalization. Most interventions focus on intensive care units. Data on interventions involving patients' personal care providers in hospitalwide settings are limited. To evaluate the impact of department-level NBSI investigations on infection incidence. Beginning in 2016, positive cultures, classified as suspected of being hospital acquired, were prospectively investigated by patients' unit-based personal healthcare providers using a structured electronic questionnaire. After analyzing the conclusions of the investigation, a summary was sent quarterly to the departments and to hospital management. NBSI rates and clinical data during a 5-year period (2014-2018) were calculated and compared before and after the intervention (2014-2015 versus 2016-2018), using interrupted time-series analysis. Among 4,135 bloodstream infections (BSIs), 1,237 (30%) were nosocomial. The rate of NBSI decreased from 4.58 per 1,000 admissions days in 2014 and 4.82 in 2015, to 3.81 in 2016, 2.94 in 2017 and 2.86 in 2018. Following a 4-month lag after introducing the intervention, the NBSI rate per 1000 admissions dropped significantly by 1.33 (P = .04; 95% CI, -2.58 to -0.07). The monthly NBSI rate continued to decrease significantly by 0.03 during the intervention period (P = .03; 95% CI, -0.06 to -0.002). Detailed department-level investigations of NBSI events performed by healthcare providers, increased staff awareness and frontline ownership and were associated with a decrease in NBSI rates hospitalwide.