The irritable bowel syndrome (IBS) and the fibromyalgia syndrome (FS) coexist in many patients. We conducted complementary studies of the prevalence of FS in IBS patients and matched controls, and of IBS in FS patients and the implications of concomitant IBS and FS on health-related quality of life (HRQOL). A study of 79 IBS patients with 72 matched controls (IBS study), and a study of 100 FS patients (FS study). All participants underwent tests of tender point sites and threshold of tenderness and answered questionnaires including personal and medical history, GI symptoms, and indices of HRQOL. In the IBS study, 25 of the 79 IBS patients (31.6%) and 3 of the 72 controls (4.2%) had FS (p < 0.001). Statistically significant differences were found among the study groups in terms of global well-being (p < 0.001), sleep disturbance (p < 0.001), physician visits (p = 0.003), pain (p < 0.001), anxiety (p < 0.001), and global severity index (SCL-90-R) (p < 0.001), with patients with IBS and FS having the worst results. IBS patients had significantly more tender points than controls (p < 0.001). In the FS study, 32 of the 100 FS patients (32%) had IBS. Patients with both disorders had significantly worse scores for physical functioning (p = 0.030) and for all but one of a 16-item quality of life questionnaire. FS and IBS coexist in many patients. Patients with both disorders have worse scores on HRQOL indices than patients with either disorder alone, or controls. Physicians treating these patients should be aware of the overlap, which can affect the presentation of symptoms, health care utilization, and treatment strategies.