Background: Tooth loss is generally considered the final outcome of oral disease. This retrospective study was performed to identify risk factors for tooth loss in patients undergoing long-term maintenance therapy. Methods: We surveyed 1145 adult patients who underwent maintenance therapy for ≥5 years after they had undergone active treatment from January 2015 to December 2016 and established a baseline status. The study variables were patient compliance, sex, number of teeth lost, cause of tooth loss, age at start of maintenance, number of remaining teeth at start of maintenance, duration of maintenance, smoking status, use of salivary secretion inhibitors, and diabetes mellitus. Additionally, 57 patients who did not undergo maintenance therapy were surveyed to examine and compare the effects of maintenance therapy. Statistical analyses were performed to assess the correlation of each variable with tooth loss. Results: The average number of teeth lost under maintenance therapy was 0.07/year. Significantly fewer teeth were lost in the maintenance than non-maintenance group. Most of the teeth lost were non-vital teeth, and the most common cause of tooth loss was tooth fracture. Patient age, number of remaining teeth at start of maintenance, use of salivary secretion inhibitors, and diabetes mellitus were related to tooth loss. Conclusions: To the best of our knowledge, this is first large-scale study of tooth loss in patients undergoing long-term maintenance therapy within a general dental clinic. Our findings demonstrate that starting maintenance therapy when patients are younger and possess more teeth may prevent future tooth loss.