A prospective clinical study was conducted to explore the possible link between peri-implant bone loss and the widespread habits of tobacco smoking and alcohol consumption. One hundred and eighty-five patients who received 514 implants were followed up for 3 years. Peri-implant marginal bone loss was evaluated by digital panoramic radiography and image analysis techniques. Multivariate analysis showed that peri-implant marginal bone loss was significantly related to a daily consumption of >10 g of alcohol, tobacco use and increased plaque levels and gingival inflammation. The present results indicate that daily alcohol consumption and tobacco use may have a negative influence on predictable long-term implant treatment outcomes, producing peri-implant bone loss and compromising restorative treatment with implant-supported prostheses.