Recently, reports of macrolide-resistant strains of Mycoplasma pneumoniae have been increasing. We examined the antimicrobial susceptibility and clinical significance in patients with M. pneumoniae. Seventy patients in whom M. pneumoniae was detected from 2008 to 2012 were included in the study, and compared with patients between 2003 and 2006. There were no macrolide-resistant strains detected in the 38 strains from 2003 to 2006, but from 2008 to 2012, out of the 70 strains 46 (65.7%) were positive for the macrolide-resistant 23SrRNA gene mutant (A2063G), which is consistent with recent trends. Comparison between cases of macrolide resistant strains and those with macrolide sensitive strains did not reveal a significant difference in the hospitalization period. The approximate duration of fever was 7 days; for both cases: those who received effective antimicrobials as the initial therapy, and for those with macrolide sensitive strains. It seems that the duration of fever depends on susceptibility to the initial antimicrobials regardless of macrolide resistance. There were some patients that improved without use of quinolone or minocycline, though macrolide-resistant strains were detected. These patients did not reveal extension of the hospital stay nor aggravation of pneumonia. This suggests that a macrolide drug might be the first choice drug for M. pneumoniae even now, and a change of drug should be considered when fever duration is long.