PURPOSE: Oral cancer diagnosis and treatment could influence the well-being of patients. The aim of this study was to assess the quality of life (QOL) of oral cancer patients after their treatments. METHOD: In this descriptive-analytical study, all oral cancer patients' records were retrieved from the archives of the oral pathology departments of Isfahan dental school and Sayed-al-Shohada from 2004 to 2015. Telephone interviews were conducted to collect data using the short form 36 (SF-36) and Head and Neck (H&N35) questionnaire. Demographic information of participants as well as tumor-related information, including last treatment date, therapy method, differentiation grade (mild, moderate, poorly differentiated), primary place of tumor in the mouth, and history of recurrence were recorded. Analysis of variance (ANOVA), t test, and Pearson and Spearman correlation coefficients were used for data analysis (α = 0.5). RESULTS: From 223 registered patients, 73 were available. Most of the participants were in the age group of 29-87 years (61 ± 16.3). The mean of SF36 and H&N QOL was 63.77 ± 23.44 (from 100) and 63.7 ± 15.36 (35-140). Females and those receiving combined therapy had lower QOL status. Participants who received their last treatment earlier had a significantly better QOL for both scores (P value < 0.001). History of recurrence, older age, and lower education had a significant correlation with general and disease specific QOL (P value < 0.001). CONCLUSION: The general QOL of patients with oral cancer was lower than that of the normal population in most domains. The postoperative QOL in our patients was significantly influenced by demographic and tumor-related factors. These factors should be considered by the treatment teams.