: On the basis of the benefits of antihypertensive treatment, progressively intensive treatment is advocated. However, it remains controversial whether intensive blood pressure control might increase the frequency of serious adverse events (SAEs) compared with moderate control. This review assessed the occurrence of SAEs in blood pressure treatment with predefined blood pressure targets. Seven original studies and eight post hoc analyses (derived from two original studies) met the inclusion criteria. Compared with moderate blood pressure treatment, intensive treatment was associated with a significant increase in treatment-related SAEs (Sign-test: P = 0.0002, Wilcoxon signed-rank test: P = 0.001). However, comparability between studies was limited, due to unclear determinations about the treatment-relatedness of adverse events, missing definitions of SAEs and variations in recording methods. Thus, a meta-analysis was not justified. The definitions of serious adverse events and methods of recording and reporting need to be improved and standardized to facilitate the comparison of results.