OBJECTIVE The aim of the study was to confirm the superior efficacy of estriol containing pessaries compared to placebo in the treatment of vaginal atrophy. METHODS In a prospective, multicenter, randomized, placebo-controlled, double-blind study, 436 postmenopausal women with vaginal atrophy (vaginal maturation index, VMI<40%; vaginal pH>5; most bothersome symptom, MBS≥65 on visual analogue scale, VAS) were treated with pessaries containing either 0.2mg estriol (N=142) or 0.03mg estriol (N=147) or with a matching placebo (N=147) for 12 weeks. METHODS Primary efficacy endpoints included increase in VMI, decrease of the vaginal pH value and decrease in intensity of MBS after 12 weeks of treatment. RESULTS The increase in VMI was significantly greater under 0.2mg estriol and 0.03mg estriol (46.3±17.0 and 38.4±19.4, respectively) compared to placebo (23.9±21.5; p values<0.001), vaginal pH decreased significantly more (-1.6±0.8 and -1.4±0.9, respectively) compared to placebo (-0.6±0.8; p values<0.001) and MBS intensity (VAS) declined significantly more (-52.2±23.7 and -47.1±23.4, respectively) compared to placebo (-31.8±26.3; p values<0.001). Adverse events were rare and occurred at similar rates in all three groups. CONCLUSIONS Superiority of estriol containing pessaries over placebo was shown in the local treatment of vaginal atrophy. Even a very low dose of 0.03mg estriol proved sufficient for local treatment of vaginal atrophy with excellent tolerability.