Aim Although methicillin‐resistant Staphylococcus aureus (MRSA) is commonly isolated from respiratory specimens in healthcare‐associated pneumonia (HCAP), it is difficult to determine the causative pathogen because of the possibilities of contamination/colonization. The present study aimed to identify clinical predictors of the true pathogenicity of MRSA in HCAP. Methods Patients with HCAP with positive MRSA cultures in the sputum or endotracheal aspirates who were admitted to Seirei Mikatahara General Hospital, Hamamatsu, Japan, from 2009 to 2014 were enrolled. According to the administered drugs and the treatment outcomes, patients with true MRSA pneumonia (MP) and those with contamination/colonization of MRSA (false MP) were identified. Baseline characteristics were compared between groups, and clinical predictors of true MP were evaluated by logistic regression analyses. Results A total of 93 patients (mean age 78.7 ± 12.6 years) were identified and classified into the true MP (n = 16) or false MP (n = 77) groups. Although baseline characteristics were broadly similar between groups, the true MP group had significantly more patients with PaO2 ≤ 60 Torr/pulse oximetry saturation ≤90% and those with MRSA single cultivation. Both variables were significant predictors of true MP in multivariate analysis (odds ratio of PaO2 ≤ 60 Torr/pulse oximetry saturation ≤90%: 5.64, 95% confidence interval 1.17–27.32; odds ratio of MRSA single cultivation: 4.76, 95% confidence interval 1.22–18.60). Conclusions Poor oxygenation and MRSA single cultivation imply the true pathogenicity of MRSA in HCAP with positive respiratory MRSA cultures. The present results might be helpful for the proper use of anti‐MRSA drugs in this population. Geriatr Gerontol Int 2017; 17: 456–462.