Universal adhesives (UAs) often exhibit comparable or even superior bond strength to traditional adhesive systems, ensuring reliable and long-lasting adhesion between the resin composite and the tooth structure. Therefore, this study aimed to assess the clinical performance of UAs compared to other adhesive systems in direct resin composite restorations through a systematic review and meta-analysis. Two reviewers executed a literature search in five electronic databases: PubMed, EMBASE, Scopus, Web of Science, and Scielo. Clinical trials comparing the clinical evaluation of resin composite restorations in Class I, Class II, or Class V cavities placed with an universal adhesive (UA) system against resin composite restorations placed with another non-UA system were included in the review. An analysis was carried out using Review Manager software version 5.3.5 (London, England, United Kingdom). Standardized effect sizes with 95% confidence intervals were calculated to allow comparisons between different interventions and different outcomes. The methodological quality of each study was assessed using the Cochrane RoB2 tool for randomized clinical trials. A total of 2331 potentially relevant studies were identified. After title and abstract examination, 14 studies remained in the systematic review. From these, a total of 11 studies were included in the meta-analysis. The retention rates of resin composite restorations after 6 months showed no significant difference between total-etch (TE, p=0.83), or self-etch (SE, p=0.78) adhesives and UAs applied in TE and SE modes (p>0.05). However, UAs applied in selective-enamel etching (SEE) mode demonstrated superior clinical performance compared to other adhesives (p=0.01), particularly TE adhesives (p=0.02). Similarly, after >12 months of follow-up, there were no significant differences in retention rates among different adhesive modes (p>0.05). Additionally, the incidence of secondary caries did not significantly differ across adhesive modes at both 6-month and >12-month evaluations (p>0.05). This systematic review and meta-analysis suggested that UAs demonstrate comparable clinical performance to TE and SE adhesive systems in direct resin composite restorations, particularly in terms of restoration retention rates and the incidence of secondary caries. UAs applied in SEE mode exhibited superior clinical outcomes compared to other adhesive systems. These findings indicate that UAs can be considered a viable alternative to traditional adhesive systems in clinical practice, offering flexibility in application while maintaining comparable long-term outcomes.