Objective: This prospective clinical study evaluated the clinical performance of one-, two- and multi-surface composite resin inlays over a 12-year period on premolars and molars. Method and materials: One clinician placed 113 indirect composite resin inlays (Signum, Heraeus Kulzer) in 30 patients that were bonded using a three-step bonding system and composite resin luting cement. Evaluations were made at 3 and 12 years by another clinician who was not involved in the placement of the restorations, using the modified US Public Health Service (USPHS) criteria. Data were analyzed using a nonparametric statistical test (Mann-Whitney U test) followed by Bonferroni correction (alpha = .05). Results: Fourteen patients could not be followed, yielding to the follow-up of 99 restorations. After 12 years, compared to the 3-year follow-up, tooth integrity, secondary caries, and sensitivity criteria showed significant change, while other parameters did not show significant difference (P > .05). Parameters such as loss of marginal integrity, loss of restoration integrity, loss of surface polish, and secondary caries received more frequently delta scores. At the 3-year follow-up, the clinical performance of one- or two-surface inlays did not show significant difference from multi-surface ones (P = .6317), but at the 12-year follow-up, the results were more favorable for multi-surface inlays. Overall, the failure rate at 12 years was 12%. Conclusions: Adhesively bonded indirect composite resin inlays showed acceptable long-term clinical results in terms of function, but surface and margin characteristics changed over time. Keywords: adhesion, composite resin, indirect composite, inlay, restorative dentistry