Coronary microvascular dysfunction (CMD) is well-known cause of angina, yet treatment options remain limited. This systematic review and meta-analysis examines the current literature and provides a contemporary evaluation of treatments using a stringent definition for CMD with accurate methods of microvascular assessment in accordance with recent consensus guidelines. Methods and Results: A search strategy was conducted independently by two authors (CK and RR). Studies were required to be prospective trials in adult patients with documented CMD by IC doppler wire, thermodilution techniques, or perfusion imaging via PET/MRI. CMD was defined as either coronary flow reserve (CFR)/myocardial perfusion reserve (MPR) <
2.5, and/or index of microvascular resistance (IMR) >
25. Methodological quality of studies was assessed via the Cochrane Risk of Bias tool. The primary and secondary endpoints were change in CFR/MPR/IMR and change in Seattle Angina Questionnaire (SAQ) scores respectively. Two-sided p-values were used and considered significant if p <
0.05. A total of 11,360 records were identified, from which 14 were included in this review covering 9 different treatments. Two treatments (quinapril and ranolazine) showed significant improvement in both CFR and angina. Three ranolazine trials were pooled in meta-analysis. The standardised mean difference showed a weak positive effect (0.24) with wide intervals (-0.21 to 0.26) which was not statistically significant (p = 0.20). We subsequently reviewed all treatments as mentioned in recent European consensus statements. Conclusions: The overall quality of evidence surrounding treatments for CMD is of "low", with lack of robust data highlighting the dire need for higher quality trials in this area.