Left-handedness has been associated with increased fracture risk in a small number of previous studies. This study reports risks for fractures at the proximal humerus, distal forearm, pelvis, foot, and shaft of the tibia/fibula according to handedness in a case-control study conducted from October 1996 to May 2001 among members of Northern California Kaiser Permanente. Handedness was assessed by questionnaire for 2,841 cases and 2,192 controls, and subjects were categorized as left-handed, right-handed, ambidextrous, or forced to switch from the left to the right hand. Compared to right-handedness, left-handedness was most strongly associated with an increased risk for proximal humerus fractures (adjusted odds ratio (OR)=2.00, 95% confidence interval (CI) 1.33 to 3.01) and less definitively with fractures of the distal forearm (adjusted OR=1.28, 95% CI 0.92 to 1.80), foot (adjusted OR=1.17, 95% CI 0.82 to 1.65), and pelvis (adjusted OR=1.40, 95% CI 0.71 to 2.74). Ambidextrous individuals had elevated risks for fractures of the distal forearm (adjusted OR=2.99, 95% CI 1.42 to 6.30), foot (adjusted OR=2.59, 95% CI 1.13 to 5.97), shaft of the tibia/fibula (adjusted OR=3.91, 95% CI 1.01 to 15.17), and proximal humerus (adjusted OR=2.37, 95% CI 0.85 to 6.65) when compared with right-handed individuals. Those individuals forced to use the right hand demonstrated no increased risk for fractures at any site. These results suggest that handedness does influence fracture risk, but the reasons for this increased risk are unclear.