The aim of this descriptive, cross-sectional study was to analyse health-related quality of life (HRQoL) in a population-based sample of people with multiple sclerosis (PwMS) in Stockholm County, with respect to disease-related and sociodemographic factors and coping capacity. A further aim was to compare our results on HRQoL--collected by face-to-face interviews at home-visits--with the results from a study with a mail-surveyed sample of PwMS in Stockholm. Home visits were made to 166 PwMS with clinically definite MS. Data were obtained from structured interviews using the Sickness Impact Profile (SIP), EuroQol-5D (EQ-5D) and the Sense of Coherence Scale. HRQoL was widely affected, especially in home management, walking and recreation. Self-rated HRQoL was worse in PwMS, including those with milder disease and shorter disease duration, than in the general population. Factors that were independently associated with large impact on HRQoL were disease severity, work status and coping capacity. The EQ-5D score of PwMS was more favourable when assessed by face-to face interviews at home in our study than in the study using mailed questionnaires. The study gives detailed information on HRQoL and will contribute to the base needed for organizing health care services aimed at improving HRQoL of PwMS in Stockholm.