The aim of this study was to evaluate the efficacy of vaginal misoprostol for cervical priming at doses of 200 mcg and 400 mcg, 12 to 15 hours before diagnostic office hysteroscopy (OH) without anesthesia in patients with infertility. Sixty infertile patients requiring a diagnostic office hysteroscopy for investigation of infertility were included in the study. The patients were randomly allocated into 3 vaginally administered misoprostol groups: (1) control group, (2) 200-mcg dose group, and (3) 400-mcg dose group. Misoprostol significantly facilitated the procedure of OH: cervical entry was easier; procedural time was shorter; baseline cervical width was larger; and pain scoring was lower in the misoprostol groups compared with the control group. Increasing the dose of misoprostol from 200 mcg to 400 mcg did not improve the effect on cervical dilation. Misoprostol is a promising analog to use for cervical priming before OH. Since doses of 200 mcg and 400 mcg vaginal misoprostol 12 hours before the OH both have proven to be effective regimens, 200 mcg may be preferred. However, before routine clinical usage, further research is needed through large, randomized, controlled trials powered to detect a difference in complications to determine whether misoprostol reduces complications in OH.