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Background: Rapid diagnosis and identification of pathogens are pivotal for appropriate therapy of blood stream infections. The T2Bacteria^®Panel, a culture-independent assay for the detection of <i>Escherichia coli</i>, <i>Enterococcus faecium</i>, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, and <i>Pseudomonas aeruginosa</i> in blood, was evaluated under real-world conditions as a point-of-care method including patients admitted to the internal medicine ward due to suspected blood stream infection. Methods: Patients were assigned to two groups (standard of care—SOC vs. T2). In the SOC group 2 × 2 blood culture samples were collected, in the T2 group the T2Bacteria^®Panel was performed additionally for pathogen identification. Results: A total of 94 patients were included. Pathogens were detected in 19 of 50 patients (38%) in the T2 group compared to 16 of 44 patients (36.4%) in the SOC group. The median time until pathogen detection was significantly shorter in the T2 group (4.5 h vs. 60 h, <i>p</i> < 0.001), as well as the time until targeted therapy (antibiotic with the narrowest spectrum and maximal effectiveness) (6.4 h vs. 42.2 h, <i>p</i> = 0.043). Conclusions: The implementation of the T2Bacteria^®Panel for patients with sepsis leads to an earlier targeted antimicrobial therapy resulting in earlier sufficient treatment and decreased excessive usage of broad-spectrum antimicrobials.