We determined the prevalence of human metapneumovirus (hMPV) infection in adults with asthma who were prospectively enrolled after hospitalization for an acute asthma exacerbation. Nasal wash specimens collected at admission and 3 months after discharge were tested for hMPV by real-time reverse-transcription polymerase chain reaction assays. hMPV was detected in 7 (6.9%) of 101 subjects at hospitalization and in 1 (1.3%) of 75 subjects at follow-up (odds ratio, 7 [95% confidence interval, 0.9-312]; P=.03). None of the patients with hMPV infection at hospitalization tested positive at follow-up, strongly suggesting that hMPV plays a direct etiologic role in acute asthma exacerbations.