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AIMS: Intensive systolic blood pressure (BP) control is associated with a lower risk of cardiovascular disease (CVD) but an increased risk of worsening renal function (WRF). This study aimed to investigate whether intensive BP control should be continued after WRF. METHODS AND RESULTS: We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Worsening renal function was defined as an estimated glomerular filtration rate decline of ≥30% during follow-up from baseline. The associations between WRF, efficacy and safety outcomes, and BP treatment were evaluated using time-updated Cox proportional hazard models. Among 9211 participants included in this analysis, 1310 participants (14.2%) experienced WRF during follow-up. The intensive BP treatment significantly reduced the risk of the primary outcome compared with the standard BP treatment among patients with WRF [hazard ratio (HR): 0.54; 95% confidence interval (CI): 0.32-0.90] and without WRF (HR: 0.82; 95% CI: 0.68-0.98; Pinteraction = 0.224). In addition, the intensive BP treatment significantly reduced the risk of all-cause death among patients with WRF (HR: 0.40; 95% CI: 0.23-0.68), but not among patients without WRF (HR: 0.84; 95% CI: 0.67-1.07; Pinteraction = 0.046). Risks of safety events were similar between BP treatment groups among patients with and without WRF. Results were similar among participants who experienced WRF early or late during the intervention. CONCLUSION: Intensive BP treatment increased the risk of WRF compared with standard BP treatment. However, intensive BP treatment was associated with reduced risks of CVD and all-cause mortality compared with standard BP treatment in patients experiencing WRF, without increasing adverse events. The relationship between intensive blood pressure (BP) treatment and the subsequent efficacy and safety outcomes in participants with or without worsening renal function (WRF) during intervention remains inconclusive.Previous studies have demonstrated that patients with intensive BP lowering treatment experienced WRF more frequently compared with patients receiving standard BP lowering treatment, and patients experiencing WRF were at heightened risks for developing subsequent cardiovascular disease (CVD) outcomes or all-cause death.In the current study, we found that intensive BP control was associated with a significant risk reduction in CVD outcomes, without an increase in adverse events compared with standard BP control, among both patients experiencing and not experiencing WRF.Findings from the current study suggest that continued intensive BP treatment in patients experiencing WRF may be beneficial for cardiovascular outcomes and may not lead to an increased risk of adverse events.