High sympathetic tone and cardiac autonomic neuropathy (CAN) are associated with major adverse cardiac events (MACE). We have shown ranolazine (RAN) improves autonomic function. RAN was introduced to 51 successive anginal CD patients (RANCD). A control group of 54 successive nonanginal CD patients (NORANCD) continued baseline therapy. Mean study duration was 6.1 years, which included semi-annual autonomic function measures (ANX 3.0, ANSAR Medical Technologies, Inc., Philadelphia, PA) and yearly myocardial perfusion SPECT studies (MPI). MACE were experienced by 29% RANCD patients versus 46% NORANCD patients (p = 0.0105). The patients from both groups with abnormal parasympathetic and sympathetic (P&S) measures and MACE totaled 52 of those patients with MACE versus 17% of those patients without MACE (p = 0.0274). Abnormal MPI was demonstrated in 35% of those with abnormal (P&S) measures and MACE versus 12% without MACE. Sympathovagal balance (SB) was lower, indicating higher, relative parasympathetic tone (known to be cardioprotective) in the RANCD group. Acute coronary syndromes occurred 4.5 times as often in NORANCD patients. High SB occur more frequently than abnormal MPI in CD patients experiencing MACE. In addition to increased myocardial blood flow as its proposed mechanism of angina relief, RAN improves P&S measures, a potentially new mechanism whereby RAN improves outcomes.