OBJECTIVES: Non-tuberculous mycobacterial pulmonary disease (NTMPD) is a debilitating rare disease. Therapy consists of a long-term course of multi-drug antibiotic regimen. Eradication of infection is the key microbiological therapy goal. We aimed to estimate the impact of sputum culture conversion to negative on the resource use among NTMPD patients without cystic fibrosis who were infected with Mycobacterium Avium Complex(MAC) and were refractory to first line therapy. METHODS: We collected data from newly diagnosed and existing patients over a 24-month period through a retrospective observational study of physicians in Canada, France, Germany, and the United Kingdom (UK). Qualified physicians provided anonymized data on NTMPD-related treatment history from patient charts. We summarized resource use during three distinct phases of NTMPD: 1) while having positive sputum culture, 2) from time of first negative sputum culture to cured (persistently negative sputum culture for 12 months after conversion to negative); and 3) while cured. We applied UK unit costs for the sample pooled across countries to estimate the direct medical costs in each phase. RESULTS: In total, 63 physicians provided data on 182 patient cases. Average follow-up per patient was 1.5 years: 229 person years among 173 patients while positive; 38 person years among 56 patients between negative culture conversion and cure; and 18 person years among 29 patients while cured. While culture positive, patients had more hospitalizations, emergency department visits, and laboratory tests, and a highest average total direct medical costs, including treatment. In the pooled cohort, mean monthly costs were £970 (median £548) while positive, £243 (median £131) while negative, and £199 (median £47) while cured. The data were skewed by high costs associated with hospitalizations. CONCLUSIONS:  Managing patients with negative sputum culture or those cured of NTMPD caused by MAC cost less than of patients with positive sputum culture.