Aim: The aim of this study was to analyse gender differences in wellbeing, as related to work status, among working-age people with severe impairments. Methods: This study is based on register and survey data for a sample of 7298 persons, drawn from the entire Swedish population of 15,515 working-age people 16–64 years old who, at the end of 2010, received Sweden’s unique personal assistance allowance, an allowance paid from the Swedish Social Insurance Agency (SSIA) to persons with severe impairments, enabling them to pay for assistants to support them in the functions of daily life. Logistic regression models were used to estimate the strength of relations between six measures of wellbeing, work status (not working, irregular work and regular work) and gender, together with key confounders. Results: Of the persons surveyed, 21% responded that they had regular work. Gender differences were found for all confounders, except for age. They were mostly in favour of men, which could reflect the general pattern in the labour market at large. Our results indicated there are substantial differences between non-working, irregularly working and working persons for several wellbeing aspects. Conclusions: This study analyses the contributions to wellbeing of work participation among working-age people with severe impairments, with a focus on gender differences. The analysis shows that work is an important determinant of the six measures of wellbeing examined, where the relationship between work participation and wellbeing is especially strong for peoples’ perceived standard of living. This major finding holds for both genders; however, the data show gender imbalance, in that compared with women, there was a larger percentage of men with severe impairments who have regular work. Future research should focus on finer distinctions between the types of work and the value added of personal assistants in the work context. Measures of general health not available for this study are needed to filter out a clearer picture of the interaction of work and well-being. Despite drawbacks, this study is nevertheless path-breaking in its focus on the value of work participation for the well-being of persons with severe impairments. For this reason, it provides a valuable extension of our knowledge and a clear point of departure for future studies.