BACKGROUND: Mastitis is a common infectious disease during lactation, and the main etiological agents are staphylococci, streptococci, and/or corynebacteria. The efficacy of oral administration of Lactobacillus fermentum CECT5716 or Lactobacillus salivarius CECT5713, two lactobacilli strains isolated from breast milk, to treat lactational mastitis was evaluated and was compared with the efficacy of antibiotic therapy. METHODS: In this study, 352 women with infectious mastitis were randomly assigned to 3 groups. Women in groups A (n = 124) and B (n = 127]) ingested daily 9 log(10) colony-forming units (CFU) of L. fermentum CECT5716 or L. salivarius CECT5713, respectively, for 3 weeks, whereas those in group C (n =101) received the antibiotic therapy prescribed in their respective primary care centers. Results. On day 0, the mean bacterial counts in milk samples of the 3 groups were similar (4.35-4.47 log(10) CFU/mL), and lactobacilli could not be detected. On day 21, the mean bacterial counts in the probiotic groups (2.61 and 2.33 log(10) CFU/mL) were lower than that of the control group (3.28 log(10) CFU/mL). L. fermentum CECT5716 and L. salivarius CECT5713 were isolated from the milk samples of women in the probiotic groups A and B, respectively. Women assigned to the probiotic groups improved more and had lower recurrence of mastitis than those assigned to the antibiotic group. Conclusions. The use of L. fermentum CECT5716 or L. salivarius CECT5713 appears to be an efficient alternative to the use of commonly prescribed antibiotics for the treatment of infectious mastitis during lactation. ClinicalTrials.gov identifier. NCT00716183.