INTRODUCTION:: The multipurpose vaginal pH-regulator (MVP-R) is a water-based, petroleum-free vaginal gel which is acid-buffering and under investigation for prevention of pregnancy and sexually transmitted infections. We assessed treatment adherence in a phase 3 contraceptive trial comparing the MVP-R and nonoxynol-9 (N-9) spermicidal gel. METHODS:: This randomized, open-label, non-inferiority study was conducted at 62 sites in the U.S. and Russia; all sites obtained IRB-approval and all subjects provided informed consent. The MVP-R (Amphora®, formerly known as Acidform) and N-9 were provided in pre-filled, single-use applicators. Women were instructed to use 1 applicator immediately before or up to 1 hour before vaginal intercourse, and to reapply product if more than 1 hour elapsed and for additional intercourse within 1 hour. Subjects recorded product use and coital activity on a daily diary. RESULTS:: The 3,324 enrollees included 1,665 MVP-R and 1,659 N-9 subjects. Baseline characteristics were similar between treatment arms; characteristics of the overall Intent-to-Treat population included mean age 27.6±5.6 years, body mass index 27.8±8.0 kg/m2 (32.8% obese), 62.0% White, and 76.6% non-Hispanic. The study method was used as the only contraceptive method and used correctly in 85.6% of coital acts (85.9% MVP-R, 85.3% N-9). Overall, 61.5% of all subjects (63.0% MVP-R, 60.1% N-9) were adherent with the proper method use for ≥90% of coital acts. The most common reason for non-adherence was failure to reapply with additional acts of intercourse within 1 hour after application (390/2,935 [13.3%]). CONCLUSION:: Most subjects used these on-demand, women-controlled products as directed. Adherence was similar between the two treatment groups.