The use of OTC analgesics is common worldwide, and the importance of the pharmacy teams is growing. Pharmacist-led medication implies that the pharmacy staff should have the necessary knowledge to deliver appropriate drugs, prevent an inappropriate drug consumption, and identify the patients in need of a medical advice. A randomized controlled study to assess the impact of training on pain knowledge and associated situations at risk among the French pharmacists and dispensers was performed. Participants were randomized into two groups receiving (n = 97) or not (n = 93) a training in the e-learning format. The training consisted of the 4 modules including the general knowledge of pain, headaches, acute musculoskeletal and chronic pain. The training modules were accompanied by the summary leaflets. The success rates were significantly higher in the trained group, with 35 % of participants reaching at least 70 % (primary endpoint) versus 2.3 % in the non-trained group. The results were not influenced by the size of the pharmacy. The knowledge improvement was more pronounced for the modules on the general knowledge of pain and headache management. For the questions associated to the risk situations, the success rates of at least 70 % were also significantly higher in the trained group The highest difference in success rates after the training was observed for the use of nonsteroidal antiinflammatory drugs during pregnancy and breastfeeding. Very low rates were obtained in both groups for the secondary headaches and the analgesic treatment adjustment in particular cases, such as chronic alcoholism or low weight. Results of this pilot study show that a training focused on pain could improve the overall knowledge of pain and suggest that it may contribute to a better pain identification, management and referral to physicians of patients at risk by the pharmacy staff in routine practice. The benefits of such a training should be assessed in a long-term prospective study, and the impact of a similar training in real-life practice remains to be evaluated.