Introduction Multimorbid chronic diseases are usually considered separately in trials. Here, we aimed to describe overall multimorbidity patterns in adults aged 55 years or older and assess their effect on health-related quality of life (HRQoL). Methods We used data for 5,647 participants included in the SUpplementation en Vltamines et Mineraux AntioXydants 2 (SU.VI.MAX 2) population-based trial. HRQoL was assessed by the French versions of the Medical Outcome Study Short Form 36 and the Duke Health Profile. An exploratory factor analysis was used to determine multimorbidity patterns, and a multi morbidity score for each resulting pattern was calculated. Adjusted multiple linear regression was used to examine the association between the identified multimorbidity and HRQoL scores by gender and for each age group (55-59, 60-64, 65-69, >= 70 years). Results More than 63% of the sample reported two or more chronic conditions (from 55.8% for those 55-59 years to 74.4% for those >= 70 years). Multimorbidity was more common among women than men (67.3% vs 60%). Two different multimorbidity patterns were identified. Pattern A was represented mainly by mental illness and bone impairments. Pattern B was represented mainly by cardiovascular and metabolic disorders. After adjusting for covariates, a high pattern A score was associated with reduced HRQoL for the physical and mental components of each HRQoL questionnaire, and a high pattern B score was associated with reduced HRQoL for only the physical component of each questionnaire. These multi morbidity scores affected HRQoL differently by age group. Conclusion Our study used a novel methodological approach to account for multimorbidity patterns in determining the link with chronic conditions. These multimorbidity scores (counted and weighted) can be used in clinical research to control for the effect of multimorbidity on patients' HRQoL and may be useful for clinical practice.