We assessed the associations between multimorbidity and health-related quality of life (HRQL), and healthcare utilization, based on 16 common self-reported chronic conditions. A cross-sectional questionnaire survey including the EQ-5D was conducted in a sample of the general population of adults (≥18 years) living in Alberta, Canada. Multiple linear and logistic regressions were used to assess the association between multiple chronic conditions and HRQL, hospitalization and emergency department (ED) use. A total of 4,946 respondents reported their HRQL, noting problems mostly with pain or discomfort (48.0%). All chronic conditions were associated with a clinically important reduction in HRQL, the highest burden with anxiety or depression (-0.19, 95% CI -0.21, -0.16) and chronic pain (-0.19, 95% CI -0.21, -0.17). Multimorbidity was associated with a clinically important reduction in the EQ-5D index score (-0.12, 95% CI -0.14, -0.11) and twice the likelihood of being hospitalized (OR = 2.2, 95% CI 1.7, 2.9) or having an ED visit (OR = 1.8, 95% CI 1.4, 2.2). Pain or discomfort is a common problem in people living with chronic conditions, and the existence of multimorbidity in these individuals is associated with a reduction in the HRQL as well as frequent hospitalization and emergency department visits.