Osteonecrosis of the jaw (ONJ) can be a severe complication of patients with multiple myeloma (MM) treated with bisphosphonates. Dental procedures are a major risk factor for ONJ occurrence. We retrospectively analysed the data of 178 patients with MM to evaluate if antibiotic prophylaxis before dental procedures may prevent ONJ. A correlation between dental procedures, antibiotic prophylaxis, incidence of ONJ and relevant clinical features was performed. Overall nine out of 178 patients developed ONJ (5 year crude cumulative incidence: 7.7%). Only one case of ONJ was not correlated with dental procedures. Seventy-five patients received at least one dental procedure and 43 received antibiotic prophylaxis. Eight cases of ONJ were observed, all in the group of patients without antibiotic prophylaxis. The only variable significantly associated with ONJ was antibiotic prophylaxis (p = 0.012), which had a protective effect. Thus, we speculated that antibiotic prophylaxis may prevent ONJ occurrence after dental procedures.