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In patients with atherosclerotic cardiovascular disease (ASCVD) under statin treatment, the influence of on-treatment level of high-density lipoprotein cholesterol (HDL-C) on cardiovascular (CV) events is controversial. Statin-treated patients were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult patients with ASCVD in Taiwan. Low HDL-C was defined as < 40 mg/dL for men and < 50 mg/dL for women. The primary outcome was a composite CV events including CV death, myocardial infarction (MI), stroke or cardiac arrest with resuscitation. A total of 3731 patients (mean age 65.6 years, 75.6% men) were included. Patients with on-treatment low HDL-C (44%, mean HDL-C 34.9 ± 6.8 mg/dL) were younger and with more diabetes and higher body weight. The mean follow-up time was 2.7 years. We used restricted cubic spline curves to examine the potential non-linear association between HDL-C and adverse outcomes. Decreased HDL-C levels were associated with a significantly increased risk of CV events in women (< 49 mg/dL in women) but not in men (< 42 mg/dL in men). However, the protective effect of elevated HDL-C levels was more prominent in men than in women. In ASCVD patients with statin therapy, low on-treatment HDL-C was common in Taiwan and associated with an increased risk of CV events in women. Higher HDL-C levels provided more protective effect in men than in women. [ABSTRACT FROM AUTHOR]