Purpose: To compare the clinical efficacy of self-adhesive Bulk-fill resin composite and traditionally bonded Bulk-fill resin composite in the restoration of proximal lesions during the course of 18 months. Materials and methods: In a parallel study design, 40 participants with carious proximal lesions were assigned at random to the intervention (Surefil-one) and comparison (Bulk-fill) groups. Two blinded assessors evaluated restorations at initial screening (1 week), 6, 12, and 18 months using modified United States Public Health Service (USPHS) criteria measuring (marginal adaptation, marginal discoloration, surface roughness, anatomic form, postoperative sensitivity, recurrent caries, color match, and retention analysis). Categorical data were described as frequency and percentage. Intergroup and intragroup comparisons were done using the Chi-squared test. Results: Intergroup comparisons of both materials after 18 months revealed no differences of statistical significance in marginal adaptation (p = 0.0952), recurrent caries (p = 0.8728), postoperative sensitivity (p = 0.5936), retention analysis (p = 0.3173), and proximal contact (p = 0.9707). There was a difference of statistical significance between both materials for marginal discoloration (p = 0.0235), color match (p = 0.007), anatomic form (p = 0.0023) after 18 months, and surface roughness after 12 and 18 months (p = 0.0013 and 0.0001, respectively). Conclusion: Over an 18-month test time frame, a self-adhesive Bulk-fill resin composite hybrid (Surefil one) revealed clinically less satisfying performance when compared to traditionally bonded Bulk-fill resin composite. Surefil one can be employed as a clinical alternative in intermediate short-term restoration of proximal lesions.