To investigate whether chronic co-contraction of the medial and lateral rectus muscles leads to higher against-the-rule astigmatism in affected versus fellow eyes in Duane syndrome. A database of 4,103 patients of Dr. Arthur Jampolsky was queried for diagnosis of Duane syndrome. Inclusion criteria were unilateral Duane syndrome and complete data set. Refractive error was compared between Duane and fellow eyes. A total of 84 patients with unilateral Duane syndrome were identified. The spherical equivalent of Duane eyes and fellow eyes was similar (0.4 vs. 0.2 [P = 0.14]). Mean cylinder power was higher in Duane eyes compared to fellow eyes (0.7 vs 0.4 [P = 0.0003]). There was modest evidence of more against-the-rule astigmatism in Duane eyes compared to fellow eyes (P = 0.04) but no difference for with-the-rule astigmatism (P = 0.83). Duane compared to fellow eyes were, however, significantly more likely to have oblique astigmatism (P = 0.004) or any astigmatism at all (P = 0.0005). Duane eyes compared to fellow eyes had higher astigmatism that was more likely to be oblique. Our study lends support to the hypothesis that extraocular muscles may influence refractive error.