Background: Operation for hemorrhoidal disease is one of the most common operations performed globally. However, we know little about the impact of the disease on health-related quality of life (HRQoL), or the importance of the observed clinical and anatomical changes. Method: This was a single-center cross-sectional and cohort study. HRQoL was assessed using the Short Form 12 and 36 (SF12 and SF36), EuroQoL 5-dimensions 5-levels (EQ-5D), and a disease specific questionnaire; Short Health Scale for Hemorrhoidal Disease (SHS_HD). SF12 and EQ-5D scores in 257 patients with symptomatic hemorrhoids referred to our proctologic outpatient clinic were compared to a Danish background population adjusting for age, gender, body mass index and educational status. Symptoms were assessed using the Hemorrhoidal Disease Symptom Score. The anatomical pathology was graded using Goligher's classification. The associations between clinical characteristics and HRQoL were tested. The impact of surgical treatment was assessed in 111 patients followed one year postoperatively. Results: Patients reporting a high symptom load had lower SF12 physical health scores compared with the background population. The EQ-5D indexes indicated impaired HRQoL in men, women <50 years and patients with higher education. Improvements in all three HRQoL measures were seen after surgery. Symptom burden had a negative association with HRQoL measures, whereas the surgeon's grading of anatomical pathology had no association. Conclusion: Hemorrhoidal disease has a negative impact on HRQoL related to the degree of symptoms. Surgical treatment improve the QoL. The surgeon's grading of anal pathology had no association with QoL.