Objective: Blood pressure (BP) lowering is accompanied by reduced cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk according to the SCORE-2 system. Design and method: A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 11/2022) for the effect of BP-lowering treatment against placebo, no treatment or less intense BP reduction on fatal or non-fatal CV outcomes. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results: We studied 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061. For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22-35%) in the category of very high-risk patients, and by 10% in the category of high-risk patients (p value for interaction = 0.020). Also, the relative risk reduction of the combined outcome was progressively greater the higher the baseline CV risk (p trend = 0.006). The risk reduction of CV death showed a significant trend from lower to higher baseline CV risk (p trend = 0.036). CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), and in the very high-risk group compared to the low-moderate risk group (p = 0.001). Conclusions: The greatest outcome benefit from BP lowering treatment in primary is observed in patients at higher baseline cardiovascular risk, as calculated by the SCORE-2.