Aim To compare the health-related quality of life of unemployed and employed women with disabilities and establish factors affecting their life satisfaction. Methods The study included 318 women with disabilities, 160 of whom were employed and 158 unemployed, paired according to age and region of residence. The health-related quality of life was assessed by The World Health Organization Quality of Life questionnaire, and social demographics and factors affecting life satisfaction were collected by a general questionnaire. The factors affecting life satisfaction were defined according to respondents’ statements. Results Unemployed women with disabilities had a lower mean score (±standard deviation) on all health-related QoL domains: psychological health (14.52 ± 2.80 vs 15.94 ± 2.55), social relationships (15.12 ± 3.08 vs 16.06 ± 2.69), environment (12.80 ± 2.78 vs 13.87 ± 2.49), as well as on a separate item of self-assessed health (3.33 ± 1.16 vs 3.56 ± 0.92) than their employed counterparts (P < 0.01). This disparity was not found only in the domain of physical health. The largest positive impact on life satisfaction in both groups was family. Conclusion As disabled women are a particularly vulnerable population group, stressing the importance of employment and family as factors affecting their quality of life may help equalizing opportunities and upgrading the quality of life of all – particularly unemployed women with disabilities.