Background:Although B blockers provide un-equivocal benefits in HF management; however some B blockers worsen insulin resistance. It will be a promising strategy to recruit such a B-blocker that did not worsen or even can improveinsulin resistance( IR). Objective: This study aimed to assess the effect of two of the third-generation B-blockers (Carvedilol versus Nebivolol) on insulin sensitivity state in non-diabetic patients with non-ischemic Cardiomyopathy with Heart Failure. Methods:43 Patients withNon-ischemic cardiomyopathy enrolled in this study were randomly assigned to receive either Carvedilol or Nebivolol after excluding Diabetes Mellitus or Myocardial ischemia. The primary endpoint was evaluating the relative effects of those two B blockers on insulin resistance as assessed by insulin resistance index(HOMA-IR) at the baseline and after three months treatment. Results: Out of 43 Patients enrolled; 58.1% % represented the Carvedilol group while 41.9% represented the Nebivolol group. Nebivolol improves insulin resistance-related variables (fasting glucose; fasting insulin; and HOMA- IR;(P< 0.001; 0.01; and 0.01 respectively.The percentage of change at HOMA-IR; indicative of insulin sensitivity status, between baseline versus at three months follow up level of intra-group comparison was increased by 4.58% at the Carvedilol arm whereas was decreased by 11.67% at the Nebivolol arm and the difference on the intra-group level of comparison was significant ( P <0.001 and 0.01) respectively Conclusion and recommendation:Nebivolol improves insulin resistance-related variables.Nebivolol may be recommended as the B - blocker of the first choice for those with of Non-ischemic Cardiomyopathy Heart Failure with evident insulin resistance however,larger scaled prospective multicenter randomized trials is needed for confirming our favorable results.