The degree of hand preference, ie, the extent to which the use of one upper extremity is obligate, has not been studied previously as a possible risk factor for the development of upper extremity cumulative trauma disorders (UECTDs). This case-control study was designed to test the hypothesis that strong hand preference, whether left or right, would be associated with UECTDs in a working population. Case subjects were drawn from workers who presented to one of two acute care clinics for treatment of work-related cumulative trauma disorders of the upper extremity. Control subjects were drawn from job applicants presenting for preplacement examinations at the same two clinics. The degree of hand preference was determined by the Edinburgh Handedness Inventory of Old-Geld.The 48 case subjects evidenced a higher absolute value of the mean handedness score (indicative of a stronger degree of hand preference) than the 134 control subjects (P = .01). As a dichotomized variable, being “strong”-handed versus “weak”-handed was a significant risk factor for UECTD (P = .01, odds ratio = 2.48). Among the 48 case subjects, 83% had a UECTD ipsilateral to the side of hand preference.This study found that workers who develop cumulative trauma disorders of the upper extremity are more likely to exhibit a strong hand preference than a group of applicants entering the work force. These findings suggest that the endogenously determined obligate use of one extremity may be a significant risk factor for the development of upper extremity cumulative trauma disorders.