Introduction: The alterations of atrial structure induced by the iterative atrial fibrillation (AFib) include renin-angiotensin-aldosterone system (RAAS) overexpression which could have a dominant role, aldosterone being involved in inflammation, fibrosis, remodeling. The objective of our study is the direct comparison of two therapeutic regimens (each one including other three subregimens), in order to assess the benefit of mineralocorticoid receptor blockers (MCRB) in repetitive AFib patients (pts). Methods: The study considered 1,152 pts with AFib, starting from 1 November 2007, structured into two comparative groups, demographically balanced (slight male and 6th decade pts predominance, respectively in both groups). The pts within the first group were treated with antiarrhythmics {Amiodarone (A) 69.69% or Propafenone (P) 22.65% or Sotalol (S) 7.66%} + MCRB, while the pts within the comparative group were treated with antiarrhythmics {A 69.69% or P 22.65% or S 7.66%} + exogenous potassium supplement (K+). We compared the occurrence of AFib episodes 24 months before and, respectively, after the initiation of treatment with MCRB. Among the exclusion criteria we notice the pts previously treated with betablockers (indirect antireninic effect), and ACE-inhibitors or ARB’s (K+ suppliers), respectively. Results: In the therapeutic arm with antiarrhythmic + MCRB, the AFib episodes decreased from 9.0+/- 2.3 24 mo. before to 3.8+/-1.9 24 mo. aft er, p < 0.005 (Subgroups: A + MCRB from 9.1+/-2.1 to 3.7+/-2.0; p < 0.01; P + MCRB from 9.0+/-2.5 to 3.9+/-2.3; p < 0.01; S + MCRB from 8.7+/-2.4 to 4.1+/-2.1; p < 0.05). In contrast, in the therapeutic arm with antiarrhythmic + K+, the AFib episodes increased from 8.9+/-2.6 to 10.4+/-2.8; p < 0.005 (Subgroups: A + K+ from 8.8+/- 1.7 to 10.5+/-2.5; p < 0.01; P + K+ from 9.1+/-2.4 to 10.3+/-1.7; p < 0.01; S + K+ from 8.9+/-0.9 to 10.3+/- 1.1; p < 0.05). Conclusions: According to our results, MCRB seems to be a valuable additional therapeutic tool in prevention AFib recurrences. No difference was found between spironolactone and eplerenone subgroups, respectively; thus, this appears as a class effect. MCRB brings up an endogenous potassium, more metabolic friendly than K+ exogenic uptake. Beyond, MCRB reduces RAAS activity and could also reduce the fibrosis involved in structural remodeling. These beneficial effects were independent of blood pressure lowering and are probably connected to the anti-inflammatory effects of MCRB.