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The influence of implant surface roughness on implant treatment outcome is still under debate. A rougher implant surface improves osseointegration but yields greater plaque accumulation and biofilm formation. Hybrid implants have a minimally rough component coronally and a moderately rough implant body. The aim of this split-mouth study is to evaluate the long-term outcome of treatment with hybrid and moderately rough implants after 6 years. As a secondary aim, Oral Health Quality of Life (OHQoL) was assessed after one and six years. Fully edentulous patients received an overdenture supported by two implants. One implant had a hybrid surface (MSC) and one implant had a moderately rough surface (DCC). Radiographic crestal bone loss (CBL), plaque score, bleeding on probing (BoP) and periodontal probing depth (PPD) were determined at one and six years. OHQoL was evaluated using the Oral Health Impact Profile-14 (OHIP-14) questionnaire and a Visual Analogue Scale (VAS). Twenty-one patients with 42 implants were evaluated after 6 years. No implants failed and a mean CBL of 0.26 mm (SD: 0.42) for the MSC group and 0.17 mm (SD: 0.29) for the DCC group was observed, which was not statistically significant. Periodontal parameters were comparable after 6 years and a significant improvement in OHQoL was observed. This randomized controlled trial concludes that hybrid implants are a predictable treatment alternative for moderately rough implants in patients with an overdenture supported by two implants.