Purpose Women with breast cancer (BC) often suffer from severe vulvovaginal atrophy (VVA) which ultimately leads to poor sexual and urinary quality of life. We conducted a prospective study among women with BC and VVA, in order to evaluate the long-term effect of laser therapy on VVA. Methods Women with BC and VVA were proposed to have fractional microablative CO 2 laser therapy (MonaLisaTouch®, DEKA) once per month for 3 months. Efficacy of laser therapy was assessed at baseline, 6 months and 18 months after treatment, using Female Sexual Function Index (FSFI) score, Ditrovie score and vaginal pH. A pap smear was also performed and the epithelial maturation pattern was noted. Paired statistical tests were used to compare results between baseline, 6 months and 18 months. Results 46 women with BC (median age interquartile range 56.5 years 47.0 – 59.4) were included between May and October 2018. PH level slightly decreased over time (mean Δ at 18 months −0.3, SD  = 0.7, p  = 0.02) whereas maturation pattern on pap smear did not change. Sexual quality of life was significantly improved at 6 months and 18 months (mean Δ at 6 months 8.3, SD  = 6.2 ( p  < 0.0001) and mean Δ at 18 months 4.3, SD  = 8.4 ( p  = 0.01)). Ditrovie total score improved at 6 months (mean Δ −1.2, SD  = 2.7, p  = 0.01) but returned to baseline afterwards. Side effects were very mild. Three women developed low (2)- and high (1)-grade HPV-linked cervical lesions during follow-up. Conclusion Among women with BC, fractional microablative CO 2 laser is effective on the long term on VVA symptoms and gynaecological quality of life. Trial registration number: ID-RCB 2018-A01500-55