This retrospective study investigated the clinical characteristics and prognostic factors of patients with disseminated infections caused by non-tuberculous mycobacteria (NTM) in Taiwan. Forty patients who fulfilled the criteria for disseminated NTM infection at a medical centre from January 2004 to December 2008 were analyzed. More than half of the patients (n = 22, 55%) were HIV-infected and fever was the most common initial presentation (n = 21, 52.5%). There were 13 episodes of co-infection with other bacterial pathogens in 11 patients (30%). The most common site of NTM isolation from culture was blood (62.5%), followed by respiratory tract (52.5%). Mycobacterium avium complex was the most common species (70%). The overall mortality rate due to disseminated NTM infection was 30%. Univariate survival analysis showed significantly higher mortality rates in female patients, patients without anti-NTM treatment and patients co-infected with other bacterial pathogens. Multivariate analysis showed that lack of anti-NTM treatment was the only prognostic factor for a poor outcome (p = 0.001). In conclusion, maintaining a high level of suspicion and starting appropriate anti-NTM treatment promptly after diagnosis are crucial to improve outcome in patients with disseminated NTM infection.