Irritable bowel syndrome (IBS) is a chronic disease that needs special self-care strategies. The current study aimed at determining the effects of a self-care program on the severity of symptoms and quality of life of patients with IBS. In this randomized controlled clinical trial, 119 patients were randomly assigned to the experimental (n = 60) and control (n = 59) groups. Patients in both groups received the usual treatment of IBS by a gastroenterologist. The control group did not receive any intervention, whereas the experimental group was trained in the self-care program. The process of implementing the self-care program included designing and determining the content validity of the self-care training package, individual training, the first follow-up call, group training, and the second follow-up call. The instruments for collecting data were IBS-Quality of Life and IBS-Symptom Severity Scale. Two sets of evaluations (before and 2 months after the intervention) were done for both groups. The data were analyzed using SPSS software, Version 16. The results showed that there was not a significant difference between the two groups in the severity of symptoms and quality of life before the intervention (p > .05); however, the 2 groups were significantly different after the intervention (p < .0001). Implementation of the self-care program resulted in the improvement of quality of life and reduction in the symptom severity in the experimental group after the intervention (p < .0001), whereas no significant changes were observed in the control group (p > .05). Hence, the data supports that self-care program was effective in improving the quality of life and reducing the severity of symptoms in patients with IBS.