Background: The objective of this systematic review and meta-analysis was: (i) to examine the association between wine consumption and cardiovascular mortality, cardiovascular disease (CVD), and coronary heart disease (CHD) and (ii) to analyse whether this association could be influenced by personal and study factors, including the participants’ mean age, the percentage of female subjects, follow-up time and percentage of current smokers. Methods: In order to conduct this systematic review and meta-analysis, we searched several databases for longitudinal studies from their inception to March 2023. This study was previously registered with PROSPERO (CRD42021293568). Results: This systematic review included 25 studies, of which the meta-analysis included 22 studies. The pooled RR for the association of wine consumption and the risk of CHD using the DerSimonian and Laird approach was 0.76 (95% CIs: 0.69, 0.84), for the risk of CVD was 0.83 (95% CIs: 0.70, 0.98), and for the risk of cardiovascular mortality was 0.73 (95% CIs: 0.59, 0.90). Conclusions: This research revealed that wine consumption has an inverse relationship to cardiovascular mortality, CVD, and CHD. Age, the proportion of women in the samples, and follow-up time did not influence this association. Interpreting these findings with prudence was necessary because increasing wine intake might be harmful to individuals who are vulnerable to alcohol because of age, medication, or their pathologies. © 2023 by the authors.Federación Española de Enfermedades Raras, FEDER; Universidad de Castilla-La Mancha, UCLM, (2022-PROD-20657); science, innovation and universities, (FPU21/06866)