The US Centers for Disease Control and Prevention recommends the initial use of rapid antigen influenza diagnostic test (RIDT) for the detection of influenza A (H1N1-09). Nasopharyngeal samples were tested from 246 patients for H1N1-09 using target-enriched multiplex polymerase chain reaction (TEM-PCR), of which 163 were additionally tested via RIDT. RIDTs had a sensitivity of 18.7% compared with TEM-PCR as the reference standard. Patients with false-negative RIDTs were withheld from 111 days of oseltamivir and 65 days of isolation. Patients negative for H1N1 via TEM-PCR had antiviral therapy immediately stopped, thereby evading 408 days of oseltamivir and 315 days of unnecessary isolation. This cost avoidance saved US$208,982.