Abstract Objective The aim of this randomized, controlled, prospective clinical trial was to evaluate the performances of two different universal adhesives and one etch-rinse adhesive for restoration of non-carious cervical lesions (NCCLs). Material and Methods Twenty patients with at least seven NCCLs were enrolled. Lesions were divided into seven groups according to adhesive systems and application modes: GSE: GLUMA Universal-self-etch, GSL: GLUMA Universal-selective etching, GER: GLUMA Universal-etch-and-rinse, ASE: All-Bond Universal-self-etch, ASL: All-Bond Universal-selective etching, AER: All-Bond Universal-etch-and-rinse, SBE (Control): Single Bond2-etch-and-rinse. A total of 155 NCCLs were restored with a nano hybrid composite (Tetric N-Ceram). Restorations were scored with regard to retention, marginal discoloration, marginal adaptation, recurrent caries and post-operative sensitivity using modified United States Public Health Service (USPHS) criteria after one week, 6, 12 and 24 months. Statistical evaluations were performed using Chi-square tests (p=0.05). Results The recall rate was 81.9% after the 24-month follow-up. The cumulative retention rates for self-etch groups (GSE: 72.2%, ASE:75%) were significantly lower than other experimental groups (GSL: 93.7%, GER: 100%, ASL: 94.1%, AER: 100%, SBE: 100%) at the 24-month follow-up (p<0.05). Regarding marginal adaptation and marginal discoloration, GSE and ASE groups demonstrated more bravo scores after 6 and 12-month observations but differences were not significant (p>0.05). Only one restoration from ASL group demonstrated post-operative sensitivity at 6 and 12-month observations. No secondary caries was observed on the restorations at any recall. At the end of 24-month observations, no significant differences were detected among groups regarding any of the criteria assessed, except retention. Conclusion GLUMA Universal and All-Bond Universal showed better results in etch-and-rinse and selective etching mode compared to the self-etch mode regarding retention. Etch-and-rinse and selective etching application modes of the current universal adhesives tended to provide better clinical outcomes considering the criteria evaluated at the end of 24-month evaluation.