Background Placement of the implant-abutment interface (IAI) away from the bone crest has been suggested to have positive impacts on maintenance of peri-implant tissues. Purpose To assess the effects of platform-switched and platform-matched implants, taking into consideration the IAI at different positions relative to the bone crest, on clinical, radiographic, and microbiological outcomes during 12 months following functional loading. Materials and Methods The present prospective randomized study was performed upon 70 patients. Group I (n = 23) implants presenting a platform-switched implant-abutment connection design was inserted 1 mm subcrestally. Group II (n = 22) implants with similar properties were inserted crestally. Group III (n = 25) implants presenting a platform-matched approach with an internal hexagon connection design was inserted crestally. The periodontal parameters were assessed at baseline, and 3, 6, and 12 months postloading. Radiographic marginal bone level (MBL) changes were analyzed at the 12-month follow-up. The amount of DNA copies of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Provetalla intermedia and total bacterial mean load in peri-implant sulcus fluid (PISF) were assessed at the same periods. Results There were no significant differences among the groups with respect to the periodontal parameters for all time periods. At 12-month follow-up, the MBL changes were 0.16 +/- 0.29 mm and 0.17 +/- 0.23 mm for group I, 0.15 +/- 0.25 mm and 0.17 +/- 0.26 mm for group II, 0.17 +/- 0.26 mm and for group III in mesial and distal sites, respectively. The mean total bacterial load was found significantly higher for group III compared to the other groups in the three interval times (P < .05). Conclusion Implants restored with platform-switching and platform-matching performed equally regarding clinical and radiographic outcomes. Platform-matched implants inserted at the crestal level presented higher the mean bacterial total load in PISF.