The prevalence of adolescent pain varies considerably across epidemiological studies, and little information is available on pain-related behaviours among adolescents, including medicine use. The aims of this study were: 1 to examine the prevalence of recurrent pain among 15-year-old adolescents in Italy; 2 to investigate the association between recurrent pain and medicine use among boys and girls; and 3 to evaluate the consistency of these associations across Regions. The World Health Organization (WHO) collaborative International Health Behaviour in School-aged Children 2013/2014 study collected self-reported data on pain and medicine use from 13611 15-year-old adolescents in 21 Italian Regions. We used multi-level multivariate logistic regression, stratified by gender, to analyse the association between recurrent pain and medicine use for headache, stomachache, nervousness and difficulties in getting to sleep. On average, across all Regions, almost 45% of adolescents reported recurrent headache, more than 30% reported recurrent backache and approximately 30% reported recurrent stomachache. Although the prevalence of both pain and medicine use was much higher among girls, the association between pain and medicine use was similarly strong in adolescents of both genders. Adolescents with recurrent pain proved more likely to use medicines also for non-corresponding pain, nervousness and difficulties in getting to sleep. The association between recurrent pain and medicine use was consistent across Regions despite large inter-regional differences in the prevalence of both phenomena. Recurrent pain in adolescence is common nationwide. Adolescents with recurrent pain are more likely to use medicines in general. Recurrent pain and medicine use should be addressed by adolescent health policies.