Purpose: To evaluate the safety and clinical efficacy of a novel surface treatment (SurfLink, Nano Bridging Molecules, Gland, Switzerland) on titanium dental implants. SurfLink consists of a monolayer of permanently bound multiphosphonic acid molecules, which mimics the surface of naturally occurring hydroxyapatite. Materials and methods: Twenty-three patients requiring at least two single dental implants had their sites randomised according to a split-mouth design to receive one titanium grade 4 implant treated with SurfLink and one untreated control implant. Additional SurfLink-treated implants were placed if needed. Implants were submerged for 3 months in mandibles and 6 months in maxillae, then loaded with definitive metal-ceramic crowns and followed for 3 years after loading. Outcome measures were crown/implant failures, any complication, radiographic peri-implant marginal bone level changes and marginal bleeding. Results: Three patients dropped out but all remaining patients were followed up to 3-years post-loading. No implant failed. Complications were reported for three patients, affecting both types of implant in two patients and only SurfLink implant in one patient. No differences for complications between the two implant types was observed (McNemar test, P = 1, difference in proportions = -0.04, 95% CI: -0.22 to 0.14). No bleeding was observed when a periodontal probe was run in the peri-implant soft tissues around any of the implants, with the exception of three implants affected by peri-implantitis. There were no statistically significant differences in marginal bone level changes between the two groups (at 3 years post-loading P = 0.86, mean difference = -0.05; SD = 1.15; 95% CI: -0.56 to 0.47). Conclusions: Medium-term data (3-years post-loading) of implants with a biomimetic monolayer of permanently bound multiphosphonic acid molecules (SurfLink surface treatment) presented no safety issues. Clinical healing in both control and SurfLink-treated implant groups was uneventful and did not differ significantly. More challenging clinical situations need to be investigated to evaluate the real effectiveness of this surface treatment.