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Although mineralocorticoid antagonists (MRAs) have been proposed as effective fourth-line blood pressure (BP)-lowering agents in resistant hypertension, this effect in hypertension at-large is unclear. We evaluated whether MRAs-mediated BP lowering is both effective and safe against controls and whether the extent of BP lowering differs between resistant hypertension and nonresistant hypertension .We searched Medline and the Cochrane Collaboration Library databases from 1991 to mid-September 2017 for randomized controlled trials (RCTs), in which MRAs were compared with placebo or other active drugs. Main outcomes were SBP and DBP lowering and treatment-related discontinuations. Continuous outcome variables were pooled as mean difference and the categorical variables as risk ratios, both with 95% confidence interval (CI). The risk of bias was assessed by using the Cochrane collaboration tool.We included 21 RCTs (2736 patients) of MRAs compared either with placebo or with active agents. Whenever all selected trials were analyzed together (MRAs versus controls), the resulting BP reduction was −7.6 (95% CI −10 to −5.3) mmHg for SBP and −2.5 (95% CI −4.2 to −0.8) mmHg for DBP, while limiting our analysis to MRAs versus placebo mean difference was increased by −2.1/−1.3 mmHg. We find no differential BP lowering between resistant hypertension and non-resistant hypertension. Treatment-related discontinuations were not different compared with either placebo or active comparators.As the extent of BP lowering following treatment with MRAs in patients with and without resistant hypertension was similar and not accompanied by increased rate of treatment-related discontinuations compared with other active comparators, these agents may have a role in BP lowering in already treated hypertensive patients who did not reach target BP values.