Background/Objectives: We aimed to compare the prescribing behavior and clinical experience of urology providers when using the combined multiplex polymerase chain reaction (M-PCR)/Pooled Antibiotic Susceptibility Testing (P-AST) diagnostic test versus the standard urine culture (SUC) in the same set of patients previously reported to have improved clinical outcomes with M-PCR/P-AST. Methods: We conducted a multi-centered, prospective, observational study (clinical trial registration: NCT05091931) with Western Institutional Review Board (IRB) approval (20214705). Adult subjects were split between the M-PCR/P-AST (n = 250) and SUC arms (n = 135). Treatment details were determined by clinician and subject surveys. Differences in prescribed antibiotics were compared using the Chi-square or Fisher’s exact test. Results: There was no significant difference in the overall use of “access” antibiotics (p = 1.0) or first-line drugs (p = 0.4483) between M-PCR/P-AST and SUC. Nitrofurantoin (p = 0.0172) and metronidazole (p = 0.0309) were more frequently used with M-PCR/P-AST, while amoxicillin/clavulanate (p = 0.0008), cefuroxime (p = 0.0378), and ertapenem (p = 0.0378) were more frequently used with SUC. Conclusions: The use of M-PCR/P-AST to guide complicated UTI management was not associated with the increased use of non-first-line antibiotics, such as carbapenems, compared to SUC. Combined with the prior reported evidence of improved patient outcomes in this same set of patients, this test should be considered for utilization when managing complicated UTI cases.