OBJECTIVE: To investigate the sex differences in cardiac autonomic modulation in patients with newly diagnosed type 2 diabetes and to determine whether cardiac autonomic modulation is associated with glycemic variability. RESEARCH DESIGN AND METHODS: We investigated a cohort consisting of 48 men and 39 women with non-insulin-treated type 2 diabetes and a known duration of diabetes <5 years. All patients were equipped with a continuous glucose monitoring sensor for 3 days, and the mean amplitude of glycemic excursions (MAGE) was calculated to obtain individual glycemic variability. Cardiac autonomic modulation was quantified by analysis of heart rate variability (HRV) in time and frequency domains and during cardiovascular reflex tests (response to standing [RS], deep breathing [expiration-inspiration], and Valsalva maneuver). RESULTS: Sex differences in age- and heart rate-adjusted HRV measures were observed in both active and passive tests. Low frequency (LF; P = 0.036), LF/high frequency (HF; P < 0.001), and RS (P = 0.006) were higher in men, whereas expiration-inspiration (P < 0.001), but not HF, was higher in women. In women, reduced cardiac autonomic modulation as assessed by the standard deviation of normal-to-normal intervals (P = 0.001), the root mean square of successive differences (P = 0.018), LF (P < 0.001), HF (P = 0.005), total power (P = 0.008), RS ratio (P = 0.027), and expiration-to-inspiration ratio (P = 0.006) was significantly associated with increased glycemic variability as assessed by MAGE. This was not the case in men. The association in women persisted in a multivariate regression analysis controlling for weight, mean heart rate, blood pressure (systolic), and triglycerides. CONCLUSIONS: In patients with newly diagnosed and well-controlled type 2 diabetes, increased glycemic variability was associated with reduced cardiac autonomic modulation in women but not in men.