Diagnosis and treatment of lung infections caused by non-tuberculous mycobacteria (NTM) remain challenging. Adherence of the clinicians to the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) 2007 guidelines is often incomplete. Between 2007 and 2014, in Grenoble Alpes University Hospital, France, 132 patients had NTM-positive cultures from lower respiratory tract (LRT) samples. We retrospectively collected diagnosis, treatment, and outcome data of patients, and evaluated the adherence of clinicians to ATS/IDSA guidelines and the consequences of patients' prognoses. Using the ATS/IDSA definitions, 31 out of 132 patients (23.5%) were considered infected, 57 out of 132 patients (43.2%) were considered colonised, 33 out of 132 (25%) were contaminated and 11 (8.4%) had missing data. Among the 31 NTM-infected patients, M. avium (23 out of 31, 74.2%) was most frequently involved. The main risk factor for NTM lung infection was underlying lung disease (30 out of 31, 96.8%). Treatment was not appropriate according to current guidelines in 58.1% of infected patients (18 out of 31). Mainly, the antibiotic treatment was installed based on radiological signs (p = 0.0006), sputum results and bronchoalveolar lavage results (p < 0.0001 and p = 0.003 respectively). Most antibiotic regimens included a macrolide (83.4%). Patients receiving appropriate treatment had the same cure rates as those receiving inappropriate treatment (p = 0.22) and similar relapse rates (p = 0.92). Current medical practices for the treatment of NTM lung infections in our institution are not consistent with the ATS/IDSA guidelines. This could potentially affect the prognosis of these patients and favour the emergence of macrolide resistance in NTM species.