OBJECTIVES: Currently, the most commonly applied approach to treatment of resistant hypertension (TRH) is adding on mineralocorticoid receptor antagonists (MRAs) such as spironolactone to existing medication therapy. Newer treatment alternatives for treating resistant hypertension were developed, however comparative effectiveness of these add-on strategies and MRAs is not established. Our objective is to perform a network-meta analysis of add-on treatment alternatives for MRAs in TRHTN and thus establish comparative effectiveness in terms of SBP and DBP reduction. METHODS: Recent meta-analyses for renal denervation (RDN) and placebo effect were supplemented with a systematic search for MRAs in TRHTN. Newer renal denervation articles were identified using Pubmed searches. Search terms included Randomized control trials (RCT), TRH, MRAs. We Independently extracted data using a pre-defined data extraction form, including Cohrane study quality indicators and the GRADE criteria. Network meta-analysis techniques were used to compare the effects of add-on treatment alternatives for TRHTN, using spironolactone as a common comparator.  RESULTS: We identified 16 articles which met our inclusion criteria. The results show that lack of add-on medication therapy leads to markedly higher blood pressure measurements than spironolactone, office SBP 24 [95% CI 2; 48] DBP 7.4 [-2.9; 18]. While add-on placebo medication results in significantly higher blood pressure than add-on spironolactone, SBP 19 [5.7; 32] DBP 8.3[2.3; 14], add-on spironolactone’s blood pressure reducing effects equal those of add-on sham operations SBP 0.58 [-28; 29] DBP 0.36 [-12; 13]. CONCLUSIONS: Currently, no active, add-on treatment strategy for TRHTN seems more effective than spironolactone. In addition, being the only effective active treatment strategy, research into future medicinal alternatives in TRHTN should use spironolactone as an active comparison, and as an obligatory background drug when investigating the effectiveness of device-based alternatives. Furthermore, trials investigating device-based alternatives such as renal denervation should always include sham procedure as a comparator.