There are few clinical studies which compare the efficacy and patient satisfaction for oral antibiotics to treat inflammatory acne. To clarify the difference between oral antibiotics, acne patients with moderate to severe inflammatory eruptions were randomized into three groups, and each patient was given minocycline (MINO), roxithromycin (RXM) or faropenem (FRPM) for 4 weeks, followed by 4 weeks of observation without any oral antibiotics. We estimated the reduction rate of inflammatory lesion counts, the scale of Skindex-16 which represents patient quality of life (QOL), and minimum inhibitory concentrations required to inhibit the growth of 90% of Propionibacterium acnes isolated from acne patients (MIC(90) ). In all three groups, inflammatory lesion counts, and emotional and total score of Skindex-16 were significantly improved (P<0.05) after 4 weeks treatment, and these effects were maintained for the following 4 weeks. Dizziness/nausea in two patients (4.1%) of the MINO group and diarrhea in three patients (5.9%) of the FRPM group were observed. There was no significant difference of percentage reduction in inflammatory lesion counts and incident rates of side-effects between these three oral antibiotics. MIC(90) of MINO was 0.25 μg/mL before and after treatment, but MIC(90) of RXM had increased from 0.25 μg/mL to more than 32 μg/mL after treatment. MIC(90) of FRPM was 0.06 μg/mL or less for all strains before and after treatment. Our randomized controlled clinical trial suggested that MINO, RXM and FRPM were efficient to improve inflammatory acne and patient QOL, and there was no significant difference between them.