BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are used to treat noncardiac chest pain (NCCP) symptoms, however, data regarding their efficacy remains inconclusive. AIM: To conduct a meta-analysis of randomised controlled trials (RCT) comparing SSRIs to placebo in patients with NCCP, and rate the quality of evidence. METHODS: Electronic databases were searched using the terms 'noncardiac chest pain', 'atypical chest pain' and 'selective serotonin reuptake inhibitors'. Data were extracted from RCTs of ≥8 weeks. Standardised mean differences (SMD), weighted mean differences (WMD) or risk ratios (RR) were used as summary statistics for pooled outcomes. GRADE methodology was used to rate the quality of evidence. RESULTS: Four RCTs (184 patients) met the inclusion criteria. Compared to placebo, patients on SSRIs showed a nonsignificant change in chest pain of 3½ points decrease on a 100 mm visual analogue scale (184 patients, 95% CI, -9.5 to 2.5; I(2)  = 0%). Change in depression scores was not significantly different between the two groups (88 patients; WMD = 0.7; 95% CI, -1.81 to 3.20; I(2)  = 64%). Treatment discontinuations were not significantly different between groups (154 patients, RR = 2.08; 95% CI, 0.77-5.60; I(2)  = 0%). The quality of evidence was rated as moderate for change in chest pain symptoms, low for change in depression scores and moderate for treatment discontinuation due to adverse events. CONCLUSIONS: Selective serotonin reuptake inhibitors are not superior to placebo in improving chest pain or depression symptoms in patients with noncardiac chest pain. Larger trials with longer follow-up periods are necessary to assess the benefits and drawbacks of SSRIs for the treatment of noncardiac chest pain.