Background: This study aimed to assess pain and quality of life in a large cohort of patients with multiple hereditary exostoses. Methods: All 322 known patients with multiple hereditary exostoses in the Netherlands were asked to participate. An age-specific questionnaire was sent to children (less than eighteen years old) and adults. The questionnaire focused on pain, daily activities, and school and/or professional situation. Adults also filled out the RAND-36 questionnaire.Results were statistically analyzed with use of the SPSS 15.0 software and with the chi-square test and multiple logistic regression. A p value of <0.05 was regarded as significant. Results: Two hundred and eighty-three patients (88%), including 184 adults (65%) and ninety-nine children (35%), completed the questionnaire. Multiple hereditary exostoses resulted in various physical and social consequences. The majority of adults (119) were employed; however, thirty-three (28%) had changed jobs because of the symptoms of multiple hereditary exostoses and twenty-five (21%) required adjustments in their working environment. Of the sixty-five adults who were not employed, thirteen were medically unfit to work. Of eighty-five children attending school, forty-five (53%) experienced problems at school. The symptoms of multiple hereditary exostoses caused twenty-seven children (27%) and eighty-five adults (46%) to stop participating in sporting activities. Pain was the greatest problem, with sixty-two children (63%) and 152 adults (83%) who reported recent pain. On multivariate analysis, pain in adults was correlated most significantly with age and problems at work, and pain in children was correlated with the perception of the disease and problems at school. Adult patients with multiple hereditary exostoses had a lower quality of life than the Dutch reference groups, with lower scores on six of eight RAND-36 subscales. Conclusions: Our study confirms that multiple hereditary exostoses is a chronic disease causing a profound impact on quality of ...