To determine through a systematic review whether HEMA-free adhesive systems have better clinical performance than HEMA-containing systems in noncarious cervical lesion (NCCL) restorations. We systematically searched PubMed, The Cochrane Library, Scopus, Web of Science, and Open Grey databases using MeSH terms, synonyms, and keywords, with no language or date restriction. The reference lists of included articles were manually searched. Randomized controlled clinical trials comparing the effectiveness of HEMA-free and HEMA-containing adhesive systems in NCCL restorations were included. The risk of bias in the included studies was assessed and classified through the Cochrane Collaboration's common scheme for bias. Quantitative data were subgrouped according to the main clinical parameters evaluated, and heterogeneity was tested using I2 index. A total of 2889 potentially relevant studies were identified. After title and abstract examination, 51 studies remained. Finally, 22 studies were included in the systematic review, totaling to 997 participants. Thus, 13 studies were classified as "low" risk of bias and nine as "unclear". These 22 studies were also included in the meta-analysis, and no significant statistical difference was found between the clinical performances of HEMA-free and HEMA-containing adhesive systems for all parameters analyzed: retention risk difference (RD) 0.03 [-0.01, 0.07] (p = 0.13); marginal discoloration RD 0.02 [-0.01, 0.04] (p = 0.19); marginal adaptation RD -0.01 [-0.04, 0.01] (p = 0.34); caries RD 0.00 [-0.01, 0.01] (p = 0.92); or postoperative sensitivity RD -0.00 [-0.02, 0.01] (p = 0.72) and for overall effect RD 0.00 [-0.01, 0.01] (p = 0.65). HEMA-free and HEMA-containing adhesive systems showed a similar clinical performance in NCCL restorations. Only the presence of HEMA does not indicate better clinical performance of adhesive systems.