Objective: The equivocal benefit of intensive blood pressure lowering in patients with diabetes may be partially due to the neglected residual cardiovascular risk. However, it remains uncertain whether residual cholesterol (RC) level affect the benefit of intensive blood pressure lowering in patients with diabetes. We aimed to determine whether the treatment difference of intensive versus standard blood pressure therapy on risk of cardiovascular events (CVD) in the ACCORD-BP trial depended on baseline RC level. Design and method: Participants in the ACCORD-BP trail were divided into two groups based on baseline RC levels (low RC: < 31 mg/dL and high RC: 31mg/dL and higher). We report the primary outcomes identical to those used in the original ACCORD trial, which included nonfatal myocardial infarction, nonfatal stroke, and/or incident cardiovascular death. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) estimated from stratified Cox regression models were used to quantify the association between intensive therapy and incident CVD for the 2 different baseline RC groups. Results: The incident rate was significantly lower in the intensive-therapy group as compared with standard-therapy group in the low RC group (log-rank P = 0.029) but not in the high RC group (log-rank P = 0.74). Compared with standard therapy, intensive therapy was associated with a lower risk of incident CVD among participants with low RC (aHR: 0.71; 95% CI: 0.53 to 0.94), but not among participants with high RC (aHR: 1.04; 95% CI: 0.80 to 1.35). The same pattern was observed for nonfatal stroke (aHR [95% CI] in participants with low RC: 0.48 [0.25-0.93]; aHR [95% CI] in participants with high RC: 0.76 [0.41-1.41]). Subgroup analyses revealed that the protective effect of intensive therapy against CVD events among the low RC group was not influenced by sex, previous CVD at baseline, assignment to intensive glycemic control, systolic or diastolic blood pressure at baseline, and baseline low-density lipoprotein cholesterol levels. Conclusions: Intensive blood pressure lowering therapy was effective at preventing incident CVD events in the ACCORD-BP trial participants with low baseline RC level but not in those with high RC level.