Aim: This prospective controlled clinical study aimed to evaluate the effect of botulinum toxin Type A (BTX-A) on pain control and quality of life (QoL) in patients with chronic myofascial pain. Materials & methods: Patients with chronic myofascial pain were randomly divided into two groups (n = 20): counseling and self-care and Michigan-type occlusal splint (MOS) (CG-control group) or BTX-A injection (BTX-AG). The pain was evaluated with visual analogue scale and QoL with the oral health impact profile-14 (OHIP-14) questionnaire. Results: In both groups, the pain was reduced, and QoL improved after 30 days. The results of social disability and handicap were better for patients treated with counseling and self-care and MOS. Conclusion: Minimally invasive strategies and BTX-A application improved QoL and alleviated myofascial pain.