Objective: The purpose of this study was to evaluate the impact of an interconception antibiotic regimen on endometrial microbial flora and histologic type. Study design: This was a secondary analysis of a double-blind randomized placebo-controlled trial of prophylactic metronidazole plus azithromycin that was given to 241 women (antibiotics, 118 women; placebo, 123 women) with a previous preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histologic types were obtained at randomization and 2 weeks after treatment. The prevalence of either the new acquisition or the resolution of individual microbes, categories of microbes, and plasma cell endometritis were compared by chi-square or Fishers' exact tests. Results: Overall, antibiotics were associated with lower acquisition and higher resolution of microbes. Of women without Gardnerella at baseline, 14% of the women who received antibiotics vs 34% of the women who received placebo had positive endometrial culture for the organism after treatment (P < .05); of those women with G vaginalis at baseline, 57% of the women who received antibiotics vs 33% of the women who received placebo (P < .05) had a negative follow-up culture. Other gram-negative rods, especially aerobes in general, manifested similar patterns. The impact on anaerobes and plasma cell endometritis was not definitive, but there was a trend toward the increased resolution of the former (77% vs 55%) and reduced acquisition of the latter (28% vs 50%). Conclusion: The antibiotic regimen prevented the acquisition and promoted the resolution, but not the eradication, of gram-negative rods such as G vaginalis and the aerobic subcategory. © 2007 Mosby, Inc. All rights reserved.