Background. The impact of neuraminidase inhibitor (NAI) treatment on clinical outcomes of public health importance during the 2009—2010 pandemic has not been firmly established. Methods. We conducted a systematic review and meta-analysis, searching 11 databases (2009 through April 2012) for relevant studies. We used standard methods conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random effects models. Results. Regarding mortality we observed a nonsignificant reduction associated with NAI treatment (at any time) versus none (OR, 0.72 95% CI, .51—1.01). However we observed significant reductions for early treatment (≤48 hours after symptom onset) versus late (OR, 0.38 95% CI, .27—.53) and for early treatment versus none (OR, 0.35 95% CI, .18—.71). NAI treatment (at any time) versus none was associated with an elevated risk of severe outcome (OR, 1.76 95% CI, 1.22—2.54), but early versus late treatment reduced the likelihood (OR, 0.41 95% CI, .30—.56). Conclusions. During the 2009—2010 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment. PROSPERO Registration. CRD42011001273.