BackgroundAmong the Pentraxins, the long Pentraxin‐3 (PTX‐3) is associated with several processes, particularly in the earliest phases of the innate humoral response. Increased blood PTX‐3 concentrations have been observed in a wide range of conditions, from infectious to cardiovascular disorders. Since its increase is more rapid than C‐reactive protein (CRP), PTX‐3 can be useful to detect and monitor early inflammation. To dissect its pathophysiological role in rheumatic diseases (RD), we conducted a systematic review and meta‐analysis comparing blood PTX‐3 concentrations in RD patients and healthy individuals and investigating possible associations with clinical, demographic, and study characteristics.MethodsWe performed a search of published evidence until April 2024 in PubMed, Web of Science and Scopus, which led to the selection of 60 relevant manuscripts from a total of 1072 records.ResultsOur synthesis revealed a statistically significant difference in PTX‐3 concentrations between RD patients and controls (standard mean difference, SMD = 1.02, 95% CI 0.77–1.26, p < .001), that correlated with CRP concentrations. The effect size was associated with geographical region of study conduction, RD type, with a reduction of the observed heterogeneity in patients with low LDL‐cholesterol and triglycerides concentrations.ConclusionsOur study has shown a significant increase in blood PTX‐3 concentrations in RD patients, which was associated with specific patient characteristics. Nevertheless, additional studies are needed to better define the utility of measuring PTX‐3 in the early phase of RD. Our study was conducted in compliance with the PRISMA 2020 statement (study protocol available at PROSPERO CRD42024516600).