BACKGROUND Children with cystic fibrosis often experience acute declines in lung function. We previously showed that such declines are not always treated with antibiotics, but we did not assess whether treatment improves the likelihood of recovery. OBJECTIVE To determine whether new antibiotic treatment was associated with recovery from acute FEV1 decline. METHODS We studied episodes of FEV1 decline (≥10% from baseline) in the Epidemiologic Study of Cystic Fibrosis. Treatments were hospitalization, home intravenous antibiotic, new inhaled oral quinolone, or other oral antibiotic. We used logistic regression to evaluate whether treatment was associated with recovery to baseline or near baseline. RESULTS Logistic regression of 9,875 patients showed that new antibiotic treatment was associated with an increased likelihood of recovery to 90% of baseline (P < 0.001), especially for hospitalization compared with no new antibiotic (odds ratio [OR], 2.79; 95% confidence interval, 2.41-3.23). All four outpatient treatments were associated with greater likelihood of recovery compared with no treatment (OR, 1.27-1.64). Inpatient treatment was better than outpatient treatment (OR, 1.94; 95% confidence interval, 1.68-2.23). Treatment-type ORs were similar across recovery criteria and levels of baseline lung function. CONCLUSIONS New antibiotic therapy, and especially inpatient treatment, is associated with greater likelihood of recovery after acute decline in FEV1. Benefits extend across all disease stages and are especially important in patients with high lung function, who are at greatest risk for FEV1 decline.