Background: Bruxism can cause masseter hypertrophy, discomfort, and facial asymmetry. Occlusal splints are widely used to manage pain and improve mandibular function, while botulinum toxin A (BTX-A) has gained interest for directly reducing masseter muscle thickness. However, the comparative effectiveness of these treatments remains unclear. Purpose: The study purpose was to measure and compare masseter muscle thickness among patients treated with occlusal splints, BTX-A, or combination, using ultrasonography. Study design, setting, sample: This randomized, nonblind clinical trial was conducted at the Department of Prosthodontics, Zonguldak Bulent Ecevit University, between April to July 2023. Subjects presenting bruxism and masseter muscle hypertrophy were enrolled. Inclusion criteria included tooth wear, clenching or grinding, masticatory pain, morning stiffness in the temporomandibular joint, and masseter hypertrophy. Exclusion criteria included active caries, acute dental pain, history of temporomandibular joint surgery, systemic or psychiatric disorders, and psychoactive medication use. Independent variable: Independent variable was treatment group; no treatment (C), occlusal splint (O), BTX-A (B), or combination splint and BTX-A (OB). Main outcome variable(s): Primary outcome was masseter thickness, measured using ultrasonography at baseline (T0), 1 (T1), 3 (T2) and 6 months (T3). Secondary outcomes included maximum incisal opening and pain intensity. Covariates: Covariates were age and sex. Analyses: Analyses conducted using SPSSv28.0 (P < .05). Two-way and repeated-measures analysis of variance were used for continuous variables; chi 2 test for categorical data. Post-hoc tests applied where appropriate. Results: A total of 48 subjects (40 females [83%], mean age 30.3 +/- 7.5 years) were included. At rest, masseter thickness significantly decreased at 1 month in B and OB groups (P < .001). This difference persisted at 3 months, with the control group showing the highest values. During contraction, significant reductions were observed at 1 month in Group O, B, and OB, while Group C remained stable. However, by 6 months, all group values had become similar in both positions, reflecting a decline in effects of treatment. Conclusions and relevance: BTX-A was more effective than splints in early masseter thickness reduction. Combination therapy offered no additional benefit. BTX-A may be minimally invasive, short-term option for managing bruxism-related hypertrophy, reducing pain and supporting individualized, costeffective care strategies. (c) 2025 American Association of Oral and Maxillofacial Surgeons