Complaints of the arms, neck, and shoulders (CANS) represent a major public health problem but the long-term course is largely unknown. Our objective was to explore the 15-year course of chronic CANS and its determinants in a population-based cohort. During 1993 to 2012, 3050 men and women aged 26 to 65 years at baseline were measured every 5 years, up to 4 times. Complaints of the arms, neck, and shoulders and sociodemographic, lifestyle, mental health, and physical load determinants were obtained by self-reported questionnaires and physical examinations. Information on chronic CANS was used to create patterns of the 15-year course: persistence, recovery, variable, no CANS, and the development of CANS. Only 47% were free of chronic CANS throughout the total 15-year period. The prevalence of other patterns was development (18.3%), persistence (8.5%), recovery (7.5%), and variable (18.7%). In multivariable logistic regression analyses, female gender, age 46 to 55 years, being not employed, former smoking, physical inactivity, an episode of CANS during the past 12 months, and high physical load in daily life (eg, often adopting awkward postures, frequent lifting, carrying, pushing, or pulling) were associated with the development of chronic CANS. Female gender, age 36 to 45 years, being not employed, and awkward postures in daily life were associated with persistent CANS. We conclude that chronic CANS represent a dynamic condition and affect the majority of the general population at least once in 15 years. Determinants associated with chronic CANS, especially physical load in daily life, can be used to develop preventive interventions and give guidance to treatment.