Purpose: to compare the efficacy and safety of 2 g amoxicillin orally with identical placebo tablets 1 hour before implant placement when placing single implants in bone types II and III. Material and methods: 12 private dental clinics in Spain agreed to participate in this trial. A total of 105 patients were recruited. Patients were randomised for consumption orally of 2g amoxicillin or identical placebo tablets. Only patients needing single implants were included. Outcome measures were post-operative infections, adverse events and implant failures. Characteristics of the saprophytic flora were also studied in all patients. Patients were seen 3 days, 10 days, 1 month and 3 months postoperatively. Results: A total of 105 patients (n = 52 in the amoxicillin group and n = 53 in the placebo group) were evaluated and none were excluded from the study at 3 months. Six post-operative infections occurred and two implants were lost in each group. There were no statistically significant differences for postoperative infection, adverse events, implant failures and the characteristics of saprophytic flora between groups. The use of amoxicillin did not either alter or modify the characteristics of the saprophytic flora nor provoke remarkable side effects. Conclusions: Antibiotic prophylaxis may not be needed when placing single implants in patients with bone types II and III. Keywords: amoxicillin, antibiotic prophylaxis, dental implants, multicentre randomised placebo-controlled clinical trial, post-operative infection