Hypotension is associated with adverse outcomes in critically ill and perioperative patients. However, these assumptions are supported by observational studies. This meta-analysis of randomized controlled trials aims to compare the impact of lower versus higher blood pressure targets on mortality. We searched PubMed, Cochrane, and Scholar from inception to February 10, 2024. Randomized trials comparing lower versus higher blood pressure targets in the management of critically ill and perioperative settings. The primary outcome was all-cause mortality at the longest follow-up available. This review was registered in the Prospective International Register of Systematic Reviews, CRD42023452928. Of 2940 studies identified by the search string, 28 (12 in critically ill and 16 in perioperative settings) were included totaling 15,672 patients. Patients in the low blood pressure target group had lower mortality (23 studies included: 1019/7679 [13.3%] vs. 1103/7649 [14.4%]; relative risk 0.93; 95% CI, 0.87-0.99; p = 0.03; I2 = 0%). This corresponded to a 97.4% probability of any increase in mortality with a Bayesian approach. These findings were mainly driven by studies performed in the ICU setting and with treatment lasting more than 24 hours; however, the magnitude and direction of the results were similar in the majority of sensitivity analyses including the analysis restricted to low risk of bias studies. We also observed a lower rate of atrial fibrillation and fewer patients requiring transfusion in low-pressure target groups. No differences were found in the other secondary outcomes. Based on pooled randomized trial evidence, a lower compared with a higher blood pressure target results in a reduction of mortality, atrial fibrillation, and transfusion requirements. Lower blood pressure targets may be beneficial but there is ongoing uncertainty. However, the present meta-analysis does not confirm previous findings and recommendations. These results might inform future guidelines and promote the study of the concept of protective hemodynamics.