Objectives: To evaluate the clinical efficacy of a Moxifloxacin (MXF)-containing regimen for the treatment of Mycobacterium avium complex (MAC) lung disease. Patients and Methods: Consecutive patients with MAC lung disease who were diagnosed between January 2002 and December 2011 were identified using the database of the NTM Registry of Samsung Medical Center. We identified 47 patients (32 males and 15 females; median age, 65 yr [IQR 56-70 yr]) who received MXF for ≥4 weeks for the treatment of MAC lung disease. Results: Thirty-two patients (68%) were treated with MXF-containing regimens because of persistent positive culture after at least 6 months of clarithromycin (CLR)-based standardized antibiotic therapy and 15 patients (32%) received MXF as a substitute for ethambutol (EMB) because they discontinued EMB due to side effect such as optic neuritis. The sputum conversion rate after MXF therapy was 34% (11/32) and 27% (4/15), respectively. The overall treatment success rate was 32% (15/47) and sputum culture conversion failed in 32 patients (68%). A positive sputum AFB smear at the start of treatment with MXF containing-regimens was an independent predictor of an unfavorable microbiologic response. Conclusions: MXF-containing antibiotic treatment for MAC lung disease can be effective in some cases. Further research is needed to study the clinical efficacy of a MXF-containing regimen for the treatment of MAC lung disease.