Complex repetitive discharges (CRDs) are a striking, infrequent finding on needle electromyography (EMG), but their significance is debated. This retrospective case-control study of 486 patients evaluated in a general hospital-based EMG laboratory examined the association of CRDs with specific diagnostic categories, duration of symptoms, and comorbid diabetes mellitus. No CRDs were identified in patients without other evidence of neuromuscular disease. Myopathy was associated with an increased risk of CRDs (adjusted odds ratio, 5.98; 95% confidence interval, 2.38 to 14.99). In general, neuropathic conditions were not associated with either an increased or decreased risk of CRDs compared with other neuromuscular diseases, although confidence intervals were wide. Similarly, neither the chronicity of symptoms nor the presence of diabetes yielded odds ratios that differed significantly from unity. In clinical populations similar to the one we studied, the positive predictive value of CRDs for any of the diagnoses we evaluated is low. However, the absence of CRDs can be of diagnostic value in that it reduces the likelihood of myopathy or motor neuron disease. The likelihood of finding CRDs in acute conditions is the same as that in chronic conditions.