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Hemiplegic shoulder pain is a common complication of stroke. The primary aim of this study was to determine the association of hemiplegic shoulder pain with health-related quality of life at 12 months after first stroke in a population-based registry. The secondary aim was to identify other factors associated with health-related quality-of-life outcomes.A prospective population-based study in a geographically defined region of Adelaide, South Australia was conducted. Multiple ascertainment methods identified all cases of stroke within a 12-month period. Objective and subjective measures were undertaken at baseline and at 4 and 12 months’ follow-up. Multiple regression analyses identified independent variables (including exposure to shoulder pain and depression, 12-month dependence, access to formal rehabilitation) associated with health-related quality of life, defined by the summary index score derived from EuroQol-5D-3L at 12 months post-stroke.Hemiplegic shoulder pain, depression, increased dependency, stroke severity, and absence of initial rehabilitation were each associated with reduction in quality of life. Age, sex, stroke type, Oxfordshire classification, and discharge destination were not related to quality of life.Hemiplegic shoulder pain reduces health-related quality of life at 12 months. More effort should be directed towards screening and management of this frequent complication of stroke.