In a sample of 5647 subjects aged 55 years or older, an exploratory factor analysis allowed for identifying two multimorbidity patterns: A and B. On exploring the cross-sectional association of individual multimorbidity and HRQoL scores (assessed by the SF-36 and DUKE questionnaires), pattern A explained more of the HRQoL score decrease than pattern B, with mean multimorbidity scores of 0.73 and 0.27 for the two patterns, respectively. HRQoL was better for men in general, and mental dimension scores tended to increase with age and physical dimension decreased.