Background: The goal of this study was to compare the two types of orthoses, prefabricated soft splints versus short thermoplastic custom-made splints, that are the most commonly used for the management of first Carpometacarpal (CMC) osteoarthritis (OA). Methods: We conducted a meta-analysis and systematic review in the literature based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We extracted the outcomes of disability scores, pain scores, grip and pinch strength and gathered the unified data accordingly. Results: We included five randomized clinical trials with 230 patients with the mean age of 61 years and the mean follow-up of 8. 1 weeks. The results of the pooled data demonstrated only a statistically significant difference in disability scores among splints in favor of the prefabricated splints. The rest of the outcome measures consisting of pain, grip strength, and pinch strength were not statistically different. Conclusion: According to our systematic review and meta-analysis, both thumb-based splints improved pain and function in the first CMC OA in a short-term follow-up, nevertheless the efficacy of prefabricated splints in abatement of disability scores was significantly higher than custom-made splints. In contrast, the other outcome measures including pain, grip and pinch strength were improved identically after wearing either of the splints.