Little information is available on the risk of fractures in patients with monoclonal gammopathy of undetermined significance (MGUS). We identified 1535 patients with MGUS between 1978 and 2003 in North Jutland County, Denmark. The population control group consisted of 15 350 persons selected from the Danish Central Population Registry, matched by age and sex. Data on fractures in the two groups were obtained from the regional Hospital Discharge Registry. In the MGUS cohort, 187 first-time fractures were identified during 9754 person-years of follow-up, corresponding to an incidence rate of 19/1000 person-years. The adjusted relative risk for fractures among MGUS patients compared with population controls was 1.4 [95% confidence interval (CI), 1.2-1.6]. After 5 years of follow-up, the risk difference was 1.8% (95% CI, 0.5-3.0). Six of the 187 MGUS patients with fractures were later diagnosed with malignant transformation. Relative risks for fractures were increased in IgG-type MGUS [1.3 (95% CI,1.1-1.6)], IgM-type MGUS [1.6 (95% CI, 1.1-2.2)] and MGUS with kappa light chain [1.4 (95% CI, 1.1-1.7)]. MGUS patients had an increased risk of fractures, which could not be explained by comorbidity, advanced age, gender or malignant transformation.