Purpose: To evaluate the efficacy of prophylactic antibiotics for dental implant placement. Materials and methods: Thirteen dentists working in private practices agreed to participate in this trial, each centre providing 50 patients. One hour prior to implant placement, patients were randomised to take orally 2 g amoxicillin or identical placebo tablets. Patients needing bone augmentation at implant placement were not included. Outcome measures were prosthesis and implant failures, adverse events and post-operative complications. Patients were seen 1 week, 2 weeks and 4 months post-operatively. Results: Two centres did not deliver any data, two centres did not manage to include the agreed quota of patients and three patients had to be excluded. Two-hundred and fifty-two patients were evaluated in the antibiotic group and 254 in the placebo group, and none dropped out at 4 months. Four prostheses and seven implants (in five patients) failed in the antibiotics group versus 10 prostheses and 13 implants (in 12 patients) in the placebo group. Eleven complications were reported in the antibiotic group versus 13 (in 12 patients) in the placebo group. No side effects were reported. There were no statistically significant differences for prosthesis failures, implant losses and complications. Patients receiving immediate post-extractive implants had an increased failure risk compared with patients receiving delayed implants (9% versus 2%). Conclusions: No statistically significant differences were observed, although trends clearly favoured the antibiotic group. Immediate post-extractive implants were more likely to fail. Keywords: amoxicillin, antibiotic prophylaxis, dental implants, immediate post-extractive implants, multicentre randomised placebo-controlled clinical trial