BACKGROUND: Hot flashes are the most commonly reported vasomotor symptom during the peri-and early post-menopausal period. OBJECTIVES: To systematically review, appraise and summarize the evidence of the impact of different SSRIs on peri-menopausal hot flashes in healthy women in randomized, controlled trials. METHODS: A comprehensive literature search was conducted of MEDLINE™, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus through March 2013. Two independent reviewers selected studies and extracted data. Random effects meta-analysis was used to pool outcomes across studies, and Bayesian mixed treatment methods were used to rank SSRIs in terms of effectiveness. RESULTS: We included a total of 11 randomized controlled trials with good methodological quality enrolling 2,069 menopausal and post-menopausal women (follow-up 1-9 months, mean age 36-76 years, mean time since menopause 2.3-6.6 years). Compared with placebo, SSRIs were associated with a statistically significant decrease in hot flash frequency (difference in means −0.93; 95 % CI −1.46 to −0.37; I 2 = 21 %) and severity assessed by various scales (standardized difference in means −0.34; 95 % CI −0.59 to −0.10; I 2 = 47 %). Adverse events did not differ from placebo. Mixed treatment comparison analysis demonstrated the superiority of escitalopram compared to other SSRIs in terms of efficacy. CONCLUSION: SSRI use is associated with modest improvement in the severity and frequency of hot flashes but can also be associated with the typical profile of SSRI adverse effects.