This study analyzed nosocomial bloodstream infections (BSIs) over three years at 49 U.S. hospitals, identifying over 10,000 cases. Gram-positive organisms accounted for 64% of cases, gram-negative for 27%, and fungi for 8%. Coagulase-negative staphylococci (32%), Staphylococcus aureus (16%), and enterococci (11%) were the most common pathogens. Enterobacter, Serratia, coagulase-negative staphylococci, and Candida were more common in critical care units. Viridans streptococci were more common in neutropenic patients. Methicillin-resistant S. aureus (MRSA) was found in 29% of isolates, and 80% of coagulase-negative staphylococci were methicillin-resistant. Vancomycin resistance in enterococci varied by species, with 50% of Enterococcus faecium resistant. BSIs remain a major cause of morbidity and mortality in the U.S., with over 250,000 cases annually. In ICU patients, the attributable mortality is 35%, with additional hospital stays and costs. Nosocomial infections are increasingly caused by antibiotic-resistant pathogens. Despite this, surveillance funding for antibiotic-resistant pathogens is less than 1% of total infectious disease surveillance funding. The SCOPE project, a nationwide surveillance network, collected data from 49 hospitals. It found that 10,617 BSIs occurred, with coagulase-negative staphylococci being the most common. Mortality rates varied by pathogen, with Candida species having the highest. The mean time from admission to BSI varied by pathogen. Critical care and ward settings had similar infection rates, but individual pathogens varied. Neutropenic patients had higher viridans streptococci infections and developed infections earlier. Antibiotic resistance varied by pathogen and geographic region. Methicillin resistance was highest in the Southeast and Northeast. Vancomycin resistance in enterococci was higher in the Northeast. Gram-negative bacteria accounted for about 25% of BSIs, with E. coli, Klebsiella, and Enterobacter being the most common. Resistance to certain antibiotics, such as ampicillin, has decreased, while ciprofloxacin and imipenem remain effective. Candida species, especially non-albicans, were significant causes of BSI with high mortality. This study highlights the importance of monitoring antibiotic resistance trends and improving surveillance for nosocomial infections. It underscores the need for increased funding and research to address the growing threat of antibiotic-resistant pathogens in hospitals.This study analyzed nosocomial bloodstream infections (BSIs) over three years at 49 U.S. hospitals, identifying over 10,000 cases. Gram-positive organisms accounted for 64% of cases, gram-negative for 27%, and fungi for 8%. Coagulase-negative staphylococci (32%), Staphylococcus aureus (16%), and enterococci (11%) were the most common pathogens. Enterobacter, Serratia, coagulase-negative staphylococci, and Candida were more common in critical care units. Viridans streptococci were more common in neutropenic patients. Methicillin-resistant S. aureus (MRSA) was found in 29% of isolates, and 80% of coagulase-negative staphylococci were methicillin-resistant. Vancomycin resistance in enterococci varied by species, with 50% of Enterococcus faecium resistant. BSIs remain a major cause of morbidity and mortality in the U.S., with over 250,000 cases annually. In ICU patients, the attributable mortality is 35%, with additional hospital stays and costs. Nosocomial infections are increasingly caused by antibiotic-resistant pathogens. Despite this, surveillance funding for antibiotic-resistant pathogens is less than 1% of total infectious disease surveillance funding. The SCOPE project, a nationwide surveillance network, collected data from 49 hospitals. It found that 10,617 BSIs occurred, with coagulase-negative staphylococci being the most common. Mortality rates varied by pathogen, with Candida species having the highest. The mean time from admission to BSI varied by pathogen. Critical care and ward settings had similar infection rates, but individual pathogens varied. Neutropenic patients had higher viridans streptococci infections and developed infections earlier. Antibiotic resistance varied by pathogen and geographic region. Methicillin resistance was highest in the Southeast and Northeast. Vancomycin resistance in enterococci was higher in the Northeast. Gram-negative bacteria accounted for about 25% of BSIs, with E. coli, Klebsiella, and Enterobacter being the most common. Resistance to certain antibiotics, such as ampicillin, has decreased, while ciprofloxacin and imipenem remain effective. Candida species, especially non-albicans, were significant causes of BSI with high mortality. This study highlights the importance of monitoring antibiotic resistance trends and improving surveillance for nosocomial infections. It underscores the need for increased funding and research to address the growing threat of antibiotic-resistant pathogens in hospitals.