Carpal tunnel syndrome (CTS) is a chronic focal mono-neuropathy caused by mechanical distortion of the nerve at the carpal tunnel. It is thought to affect between 4 and 5% of people worldwide, 50 per1000 persons in developed countries, 12.1% in east Africa and 29.2% Ethiopia. The common risk factors include but not limited to, age, sex, inflammatory conditions, pregnancy, diabetes mellitus, and hypertension. Despite this, carpal tunnel syndrome prevalence and its associated factors among patients with musculoskeletal complaints are unaddressed. Objectives This study's aim was to assess the prevalence of carpal tunnel syndrome and its associated factors among patients with musculoskeletal complaints in Dire Dawa, Eastern Ethiopia. Methodology An institution-based cross-sectional study was conducted from June 1 to 30, 2022 at Dilchora referral hospital. 265 study participants were selected using the systematic sampling technique. Interviewing techniques and physical examination of the hands and wrists were used to get the data. Epi Data version 3.1 was used to enter, clean up, and edit the data before exporting it for analysis to SPSS version 23.0 software. Bivariable and multivariable logistic regression were carried out with a 95% confidence interval to identify the association of independent and dependent variables. A P-value of 0.05 was considered statistically significant. Result A total of 260 respondents were included in this study. The prevalence of clinically proven carpal tunnel syndrome among study participants was 10.8%, with a 95% CI of (6.99 to 14.6). A multivariable analysis found that being female (AOR: 3.26 (95% CI: 1.05, 10.08), being physically inactive (AOR: 6.32 (95% CI: 1.95, 20.52), diabetes mellitus (AOR: 4.23 (95% CI: 1.47, 11.97)), hypertension (AOR: 6.07 (95% CI: 1.70, 21.65)), hand ratio <2.1 (AOR: 7.31(95% CI: 1.80, 29.66)), and wrist ratio > 0.72 (AOR: 5.94 (95% CI: 2.11, 16.72)) were statistically associated factors of carpal tunnel syndrome. But, BMI were not statistically associated with CTS. Conclusion The prevalence of carpal tunnel syndrome among patients with musculoskeletal compliant was 10.8%. Several risk factors for CTS have been identified.