Purpose of Investigation: The purpose of this study is to compare neonatal outcomes and oxidative stress markers of preterm premature rupture of membranes (PPROM) treated with third-generation cephalosporin plus metronidazole (regimen A) with those treated with third-generation cephalosporin plus clarithromycin (regimen B). Materials and Methods: The present study included patients with singleton pregnancies with PPROM at earlier than 34 gestational weeks who were admitted to the Chonnam National University, Gwangju, Korea, between February 2007 and December 2015. Latency period, neonatal outcomes, and oxidative stress markers (including oxygen radical absorbance capacity, malondialdehyde (MDA), protein carbonyl, and interleukin-6) were compared between two groups. Results: Latency period from PPROM to delivery did not differ between the groups (11.0 ± 13.1 vs. 11.5 ± 8.6, p = 0.791). However, there were no significant differences in rate of latency period longer than seven days. More women were delivered after 48 hour in the regimen B group than in the regimen A group (83.6% vs. 94.7%, p = 0.022). However, there were no significant differences in rate of latency period longer than seven days. There was no significant difference in oxidative stress markers after the administration of antibiotics between regimens A and B. Conclusion: The present results show that there was no difference between the two regimens on the latency period and improvement of neonatal outcomes. Although there was no significant difference in neonatal outcomes, the regimen using third-generation cephalosporin plus clarithromycin may have a beneficial effect for short-term prolongation of pregnancy (up to 48 hours) to allow for the administration of antenatal corticosteroids and transfer to the tertiary center.