Study ObjectiveVaginal packing is traditionally placed after pelvic floor reconstructive surgery (PFRS) to prevent hematoma formation. We seek to determine if there is a difference in post-operative pain scores after PFRS if vaginal packing is soaked with estrogen cream, bupivacaine, or saline. The primary outcome was pain as measured by a visual analog scale (VAS) at 2 hours, 6 hours, and 1 day post-operatively. Secondary outcomes include change in hemoglobin, urinary retention and length of stay (LOS) in hospital. DesignProspective cohort study SettingTertiary care academic teaching hospital. All PFRS performed by fellowship-trained urogynecologists. ParticipantsConsenting patients undergoing PFRS. InterventionsAt the completion of surgery, gauze packing soaked with either estrogen cream 0.25% bupivacaine with 1% epinephrine, or normal saline was placed inside the vagina and removed on post-operative day 1. ResultsWe included 210 patients (74 estrogen, 66 bupivacaine, 70 saline). There was no significant difference in mean post-operative pain scores between the groups (estrogen, bupivacaine, saline-soaked vaginal packs respectively) at 2 hours (2.66±2.25, 2.30±2.17, 2.24±2.07; p=.4656), 6 hours (2.99±2.38, 2.52±2.30, 2.36±2.01; p=.2181) or on post operative day 1 (1.89±2.01 vs. 2.08±2.15 vs. 2.44±2.19; p=.2832) as measured by VAS scores (0-10). There was no difference in the secondary outcomes of change in pre-/post-operative hemoglobin (21.8±10.73g/L, 20.09±11.55g/L, 21.7±9.62g/L, p=.68), urinary retention (37%, 45% and 48%, p=.45), LOS (1.05±0.46 days, 1.02±0.12, 1.03±0.24, p=.97) or in-hospital opioid usage during admission (represented in morphine milligram equivalents (median (IQR1, IQR3), Kruskal-Wallis test): 11.25mg (0,33), 7.5mg (0, 22.5) and 15mg (0, 33.88) p =0.41. ConclusionThere was no difference found between soaking vaginal packing with estrogen cream, bupivacaine, or saline after PFRS with respect to post-operative pain scores, LOS, in-hospital opioid usage, or urinary retention. Saline-soaked packing is an equivalent alternative to estrogen or bupivacaine vaginal packing. Clinical Trial RegistrationNCT03266926. Registered February 1, 2017. https://clinicaltrials.gov/study/NCT03266926