According to the literature, quality of life has been shown to be reduced in females compared with males with Inflammatory Bowel Disease (IBD). Psychosocial factors are also playing an important role in IBD, especially emotional lability. The aims of study was to investigate the sex differences in general and specific health-related quality of life (HRQoL), anxiety and depression in IBD patients. Hundred and twelve outpatients of the Gastroenterology Division, Clinical Hospital Centre Rijeka, were enrolled in our study and divided in two groups: 50 females (31 with ulcerative colitis, UC and 19 with Crohn disease, CD) and 62 males (30 with UC and 32 with CD), age range 19 to 74 (M = 41.46; SD = 13.06). Most patients have been in long clinical remission or with mild disease according to Clinical Disease Activity Index (CDAI) score for CD and Clinical Activity Index (CAI) score for UC. There were significant differences in physical (F = 13.96, p < .0001) and mental (F = 9.44, p < .001) component of the general HRQoL, emotional domain ((F = 9.26, p < .001) and bowel symptoms (F = 7.04, p < .001) of the Inflammatory Bowel Disease Quality of life (IBDQoL), as well as, in anxiety (F = 7.03, p < .001) and depression (F = 12.09, p < .0001) between men and women with IBD. Women have expressed significantly lower level of the general HRQoL and more emotional disturbances connected with their disease as well as more frequent bowel symptoms compared with men. Effect sizes of those differences were large. Results of this study confirm that women with IBD are more prone to the negative impact of the disease on their HRQoL than men. Women with higher level of depression and anxiety experienced more emotional disturbances, bowel and systemic symptoms and lower general HRQoL. These results should deserve more considerations in the clinical treatment of IBD patients.