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Objectives The EQ-5D is a self-administered questionnaire which necessitates its existence and adaptation in different languages. This study aimed to translate, cross-culturally adapt, and determine the reliability and validity of the Yoruba version of the EQ-5D questionnaire. Methods Following the International Quality of Life Assessment (IQOLA) project guidelines, the EQ-5D-5L questionnaire was first translated from the English version following a sequence of forward translation, reconciliation and harmonization, backward translation, reconciliation of problematic items. A total of 113 individuals with musculoskeletal disorders were recruited to test the validity of the Yoruba translated version of the EQ-5D-5L (EQ-5D-Yor). A seven-day test-retest reliability of the EQ-5D-Yor was carried out among 109 of the respondents. Convergent and discriminant validity of the EQ-5D-Yor were determined using the Yoruba version of the SF-12 (SF-12-Y) and Visual Analogue Scale (VAS). Data was analyzed using descriptive and inferential statistics of Pearson/Spearman correlation, Intra-Class Correlation, Cronbach alpha and multi trait scaling analysis. Alpha level was set as p < 0.05. Results The construct validity of the EQ-5D-Yor yielded Spearman rho ranging from 0.438 to 1.000, with the EQ-VAS having the highest co-efficient (r = 1.000; p = 0.001). The convergent validity of the EQ-5D-Yor index with SF-12-Y yielded no significant correlations (p < 0.05), except the physical functioning scale (r = -0.709, p = 0.001). On the other hand, the divergent validity of the EQ-5D-Yor index with VAS yielded a weak correlation, (r = 0.016). The Intra-class Correlation Coefficient and Cronbach alpha for the test-retest reliability of the EQ-5D-Yor were 1.000 and 0.968. The confirmatory factor analysis showed the factor loadings were poor when including VAS in the model. Conclusions The EQ-5D-Yor has acceptable validity and reliability and can be used as a valid tool in economic evaluation s