Purpose: Diabetes mellitus and systemic hypertension are frequently reported as ischemic causes of sixth nerve palsy/-paresis, but there are few rigorous studies to support these associations. We conducted a population-based case-control study to determine the presence and magnitude of any association of preexisting diabetes mellitus and systemic hypertension with isolated sixth nerve palsy. Design: Retrospective population-based case-control study. Participants and Controls: Participants were patients with new onset of neurologically isolated sixth nerve palsy or paresis (n=76) in Olmsted County, Minnesota, from January 1, 1978, to December 31, 1992. Controls (n=76) were selected from the same general population and were matched for age, gender, and length of medical follow-up. Methods: Using the Rochester Epidemiology Project medical records linkage system, which captures virtually all medical care provided to residents of Olmsted County, Minnesota, we identified all incident cases of neurologically isolated sixth nerve palsy/paresis (n=76) among county residents between the given dates. An equal number (n=76) of controls were randomly selected from the general population. We reviewed the entire medical record of each case and control, using stringent predetermined criteria to define the presence of diabetes mellitus and systemic hypertension. We compared the prevalence of diabetes and systemic hypertension between cases and controls by use of chi-square tests, and we calculated odds ratios (OR)with 95%confidence intervals (CI). MainOutcome Measures: Presence or absence of diabetes mellitus and systemic hypertension. Results: Diabetes mellitus occurred more frequently in cases (23.7%) than in controls (5.3%; P=0.001; OR, 5.59; 95%CI, 1.79-17.42). Systemic hypertension occurred with similar frequency in cases (51.3%) and controls (39.5%; P=0.14; OR, 1.62; 95%CI, 0.85-3.08). Coexistent diabetes mellitus and hypertension were more common in cases (18.4%) than in controls (2.6%; P=0.002; OR, 8.36; 95%CI, 1.83-38.18). Conclusions: We conclude that there is a 6-fold increase in odds of having diabetes in cases of sixth nerve palsy over controls, whereas systemic hypertension does not seem to be associated with increased odds. In contrast, there is an 8-fold increased odds of having coexistent diabetes and hypertension in cases of sixth nerve palsy over controls. The much-cited association of systemic hypertension alone with sixth nerve palsy may be coincidental. Purpose: Diabetes mellitus and systemic hypertension are frequently reported as ischemic causes of sixth nerve palsy / -paresis, but there are few rigorous studies to support these associations. We conducted a population-based case-control study to determine the presence and magnitude of any association of preexisting diabetes mellitus and systemic hypertension with isolated sixth nerve palsy. Design: Retrospective population-based case-control study. Participants and Controls: Participants were patients with new onset of neurologically isolated sixth nerve palsy or paresis (n = 76) in Olmsted County, Minnesota, from January 1, 1978, to December 31, 1992. Controls (n = 76) were selected from the same general population and were matched for age, gender, and length of medical follow-up. Methods: Using the Rochester Epidemiology Project medical records linkage system, which captures virtually all medical care provided to residents of Olmsted County, Minnesota, we identified all incident cases o f neurologically isolated sixth nerve palsy / paresis (n = 76) among county residents between the given dates. An equal number (n = 76) of controls were randomly selected from the general population. We reviewed the entire medical record of each case and control , we used the prevalence of diabetes and systemic hypertension between cases and controls by use of chi-square tests, and we calculated odds ratios (OR) with 95% confidence intervals (CI). Main Outcome Measures: Presence or absence of diabetes mellitus and systemic hypertension. Results: Diabetes mellitus occurred more frequently in cases (23.7%) than in controls (5.3%; P = 0.001; OR, 5.59; -17.42). Coicistent diabetes mellitus and hypertension were more common in cases (51.3%) and controls (39.5%; P = 0.14; OR, 1.62; 95% CI, 0.85-3.08) 18.4%) than in contConclusions: We conclude that there is a 6-fold increase in odds of having diabetes in cases of sixth nerve palsy over controls, on systemic (rols) (2.6%; P = 0.002; OR, 8.36; 95% CI, 1.83-38.18) hypertension does not seem to be associated with increased odds. In contrast, there is an 8-fold increased odds of having coexistent diabetes and hypertension in cases of sixth nerve palsy over controls. The much-cited association of systemic hypertension alone with sixth nerve palsy may be coincidental.