Purpose : Mycoplasma pneumoniae (MP) is a common pathogen of childhood pneumonia. Recently, MP pneumonia that does not respond to macrolide has increased and can sometimes cause severe clinical features. Therefore, tetracyclines, fluoroquinolones, and steroids have been proposed as alternative treatments. We aimed to compare the therapeutic efficacy of prolonged macrolide ( PMC), corticosteroid (CST), doxycycline (DXC), and levofloxacin (LFX) against macrolide-unresponsive MP pneumonia. Methods : We retrospectively analyzed medical records of MP pneumonia cases hospitalized at Gil Medical Center from January 2015 to April 2017. Macrolide -unresponsive MP pneumonia patients who were clinically defined as persistent fever≥ 38.0℃ at 72 hrs after macrolide treatment were enrolled. Cases were divided into four groups based on secondary treatments: PMC, CST, DXC, and LFX. We compared the time of defervescence after secondary treatment in each group, and collected data on their side effects in each group. Results : Among 1,248 MP pneumonia cases, 172 cases (13.8%) was unresponsive to macrolides. These macrolide-unresponsive cases was classified as PMC (n=137), CST (n=18), DXC (n=11) and LFX (n=7) groups. The time of defervescence after secondary treatment was shorter in the CST and LFX groups than in the PMC group ( P0.001 and P=0.038, respectively). Median times of defervescence after secondary treatment ( PMC, CST, and LFX) were 45.7 hrs (IQR= 20.3-71.3), 0.7 hrs (IQR= 0-10.6), and 16.5 hrs (IQR= 2.0-50.7), respectively. The time of defervescence was shorter in the DXC group than in the PMC group ( P=0.008) when both groups of patients were all ≥8 years of age. Median times of defervescence after PMC and DXC treatment among ≥ 8 years of age were 48.0 hrs (IQR= 20.0-69.7) and 16.0 hrs (IQR= 4.0-33.7), respectively. No side effect was observed among CST, DXC, and LFX groups. Conclusions : CST, DXC, and LFX can be considered as effective second-line treatments in patients with macrolide-unresponsive MP pneumonia.