Abstract Background For many adults, their role as a parent is a vital part of their lives. This role is likely to be associated with a parent’s health-related quality of life (HRQOL). The aim of this study was to explore the associations between gender, demographic and psychosocial variables, pain, and HRQOL in parents of 14–15-year-old adolescents. Methods This was a cross-sectional study that included 561 parents. Data on demographic, psychosocial variables and pain were collected using validated instruments. HRQOL was assessed using the RAND-36. Data were analysed using univariate and hierarchical multiple linear regression analyses. Results Four hundred and thirty-six (78%) mothers and 125 (22%) fathers with a mean age of 45 (SD = 5) years were included. Eighty-one per cent were married/cohabiting, 74% worked full time, and 50% had university education of more than 4 years. Almost one-third reported daily or weekly pain, and more than half (58%) reported using pain analgesics during the previous 4 weeks. Mothers reported significantly lower scores on self-efficacy, self-esteem and for all RAND-36 domains, including the physical component summary (PCS) and mental component summary (MCS) and experienced greater stress than fathers. Hierarchical regression analyses showed that working part-time (beta = 0.40) or full time (beta = 0.52) (reference: not working) had the strongest positive effect on PCS. Absence from work for > 10 days (beta = −0.24) (reference: no absence), short-term pain (beta = −0.14), chronic pain (beta = −0.37) (reference: no pain), and stress (beta = −0.10) had the strongest negative effects on PCS. High self-esteem (beta = 0.11) had the strongest positive effect, whereas stress (beta = −0.58) and absence from work for > 10 days (beta = −0.11) (reference: no absence) had the strongest negative effects on MCS. Conclusion Mothers reported significantly lower scores on self-efficacy, self-esteem, and HRQOL, and experienced greater stress than the fathers. A high proportion of parents reported pain. Pain, stress, and low work affiliation were strongly associated with decreased HRQOL in parents. We recommend that parents of adolescents should be provided guidance about coping with pain and stress, and facilitation of a strong work affiliation because these seem to be important to parents’ HRQOL.