Buruli ulcer (BU) is described as a relatively painless condition; however clinical observations reveal that patients do experience pain during their treatment. Knowledge on current pain assessment and treatment in BU is necessary to develop and implement a future guideline on pain management in BU. A mixed methods approach was used, consisting of information retrieved from medical records on prescribed pain medication from Ghana and Benin, and semi-structured interviews with health care personnel (HCP) from Ghana on pain perceptions, assessment and treatment. Medical records (n = 149) of patients treated between 2008 and 2012 were collected between November 2012 and August 2013. Interviews (n = 11) were audio-taped, transcribed verbatim and qualitatively analyzed. In 113 (84%) of the 135 included records, pain medication, mostly simple analgesics, was prescribed. In 48% of the prescriptions, an indication was not documented. HCP reported that advanced BU could be painful, especially after wound care and after a skin graft. They reported not be trained in the assessment of mild pain. Pain recognition was perceived as difficult, as patients were said to suppress or to exaggerate pain, and to have different expectations regarding acceptable pain levels. HCP reported a fear of side effects of pain medication, shortage and irregularities in the supply of pain medication, and time constraints among medical doctors for pain management. Professionals perceived BU disease as potentially painful, and predominantly focused on severe pain. Our study suggests that pain in BU deserves attention and should be integrated in current treatment. Buruli ulcer (BU) is considered relatively painless. Nevertheless, observations suggested that patients experience pain during wound care dressings. This study explored views on pain, along with pain assessment and treatment practices. Medical records were reviewed on prescribed pain medication and health care professionals involved in BU treatment were invited for an interview to elicit their views on pain including current pain practices. Interviews were held in private locations, audio-taped, and analyzed qualitatively. In the majority of medical records, pain medication was prescribed. Mostly simple analgesics were prescribed, while health care professionals reported not being trained in the assessment of mild pain, and indications were often missing. Health care professionals indicated advanced BU might be painful, and that pain can increase after wound treatment, and after a skin graft at the donor site. They perceive the recognition of pain as difficult as patients suppress or exaggerate pain, and have different expectations regarding acceptable pain levels. Finally, they indicated a fear of side effects of pain medication, a shortage of, and irregularities in supply of pain medication, and limited time among medical doctors for pain management. These findings indicate pain during BU disease deserves attention and pain practices should be integrated in standard treatment.