Purpose: To evaluate the difference between a single preoperative dose versus an additional two-day postoperative course of oral amoxicillin in patients undergoing conventional dental implant placement. Materials and methods: Two dentists in two different private practices conducted this study. One hour prior to surgery, patients had to take a single prophylactic antibiotic dose, consisting of 2 g of amoxicillin orally; after implant placement, patients were randomly allocated to two different groups: protocol A (no other antibiotic administration) and protocol B, (1 g of amoxicillin in the evening of the day of surgery and 1 g twice a day for the 2 days after). Outcome measures were prosthetic and implant failures, adverse events and early postoperative complications. Patients were followed up to 6 months after functional loading. Results: Three hundred and sixty patients were randomised and treated (192 patients in one centre and 168 in the other). Five hundred and sixty-seven implants were placed. Protocol A was applied to 180 patients (278 implants) and protocol B also to 180 patients (289 implants). Data for 17 patients, 14 from protocol A and three from protocol B, were not available. No statistically significant differences were found for the reported outcomes. Two patients of protocol B experienced a prosthetic failure, losing four implants, while no prosthetic failures were reported for protocol A (P = 0.4836; difference in proportions = -0.0110; 95% CI: -0.0412 to 0.0119). Five patients (3.0%) of protocol A lost five implants versus 5 patients (2.8%) who lost eight implants in protocol B (P = 1.0000; difference in proportions = 0.0020; 95% CI: -0.0384 to 0.0438). Three adverse events were observed in the total population, all occurring in protocol B (1.69%), with no statistically significant differences between the two groups (P = 0.1199; difference in proportions = -0.0170; 95% CI: -0.0487 to 0.0059). However, one patient experienced a severe allergic reaction requiring therapy discontinuation and hospital admission. Early postoperative complications occurred in six patients of protocol A and in four patients of protocol B, with no statistically significant differences (P = 0.5170; difference in proportions = 0.0130; 95% CI: -0.0254 to 0.0568). Conclusions: No statistically significant differences were observed between 2 g of preoperative amoxicillin and an additional 2-day postoperative course, although adverse events were reported only in the additional 2-day postoperative group. Based on these findings, it might be sufficient to routinely administer preoperatively 2 g of amoxicillin to patients undergoing routine dental implant placement procedures rather than administering additional postoperative doses. Keywords: amoxicillin, antibiotic prophylaxis, complications, dental implants