We determined the incidence, distribution, and resolution of neurologic sequelae and the association with anesthetic, surgical, and patient factors after single-injection interscalene block (ISB) using levobupivacaine 0.625% with epinephrine 1:200,000 in subjects undergoing shoulder or upper arm surgery, or both, in 693 consecutive adult patients. After a standardized ISB, assessments were made at 24 and 48 h and at 2 and 4 wk for anesthesia, hypesthesia, paresthesias, pain/dysesthesias, and motor weakness. Symptomatic patients were monitored until resolution. Subjects reporting pain or discomfort >3 of 10 and those with motor or extending sensory symptoms received diagnostic assessment. Six-hundred-sixty subjects completed 4 wk of follow-up. Fifty-eight neurologic sequelae were reported by 56 subjects. Symptoms were sensory except for two cases of motor weakness (lesions identified distant from the ISB site). Thirty-one sequelae with likely ISB association were reported by 29 subjects, including 14 at the ISB site, 9 at the distal phalanx of thumb/index finger, 7 involving the posterior auricular nerve, and 1 clinical brachial plexopathy. Sequelae not likely associated with the ISB were reported by 27 subjects with symptoms reported in the median (n = 9) and ulnar (n = 4) nerves, surgical neuropraxias (n = 12), and motor weakness (n = 2). Symptoms resolved spontaneously (median 4 wk; range, 2-16 wk) except in the two patients with motor weaknesses and the patient with clinical brachial plexopathy, who received therapeutic interventions. Variables identified as independent predictors of neurologic sequelae likely related to ISB were paresthesia at needle insertion and ISB site pain or bruising at 24 h. In contrast, surgery preformed in the sitting position, as well as ISB site bruising, was identified as a predictor of neurologic sequelae not likely related to ISB. In conclusion, neurologic sequelae after single-injection ISB using epinephrine mainly involve transient minor sensory symptoms.