Objectives. To investigate the prevalence of tooth loss and different prosthetic rehabilitations among Iranian adults, as well as the potential determinants of tooth loss. Methods. In a cross-sectional community-based study conducted among 8094 Iranian adults living in Isfahan province, a self-administered questionnaire was used to assess epidemiologic features of tooth loss. Results. Thirty-two percent of subjects had all their teeth, 58.6% had lost less than 6, and 7.2% of participants had lost more than 6 teeth. One hundred and sixty-nine individuals (2.2%) were edentulous. Among participants, 2.3% had single jaw removable partial denture, 3.6% had complete removable denture in both jaws, and 4.6% had fixed prosthesis. Others reported no prosthetic rehabilitation (89.5%). In the age subgroup analysis (≤35 and >35 years old) tooth loss was more prevalent among men than women (OR = 2.8 and 1.9, resp., P < 0.01). Also, in both age groups, current and former smokers had higher levels of tooth loss than nonsmokers (P < 0.001 and P < 0.05, resp.). In addition, tooth loss was positively related to metabolic abnormality for age group >35 years (adjusted OR = 1.29, P < 0.01). Conclusions. Tooth loss is highly prevalent in Iranian adult population. Community programs promoting oral health for prevention of tooth loss should be considered taking into account its major determinants including lower educational level, male gender, smoking, and metabolic abnormality.