Health-related quality of life (HRQoL) is a well-established aspect of health that can be measured by both disease-specific and general instruments. The effect of uncontrolled asthma on generic HRQoL has not been shown in patients with clinically confirmed adult-onset asthma and with asthma control defined according to the Global Initiative for Asthma, so the aim of this study was to determine this. In the 12-year follow-up cohort of the Seinäjoki Adult Asthma Study (n = 203), patients with uncontrolled and partially controlled asthma had lower generic HRQoL as determined by 15D compared to the controlled group. On 10 out of 15 dimensions of 15D, the mean scores were significantly lower in patients with uncontrolled asthma compared with those with controlled asthma. The affected dimensions were mobility, breathing, sleeping, usual activities, mental function, discomfort and symptoms, depression, distress, vitality and sexual activity. In the Tobit regression analysis, a poorer 15D score was associated with uncontrolled asthma, lower postbronchodilator FEV1, female sex, depression, treated dyspepsia and poorer 15D score at diagnosis. Our results show that uncontrolled asthma affects everyday life in several aspects, including previously unknown components such as sexual activity and vitality.