Thirty-four cases of childhood lymphoblastic leukemia that were complicated by CNS and peripheral thrombosis or hemorrhage associated with L-asparaginase (L-asp) therapy were reviewed to determine the effect of the events on the subsequent clinical status. There was no predilection for any site in the CNS cases; all but one of the peripheral events occurred in the lower extremities. The median time for 28 CNS and eight peripheral events from the beginning of L-asp therapy was 17 and 16 days, respectively. One patient died as a result of the CNS event. Twenty-six patients were surviving with a median follow-up of 27 months at the close of the study. Of the patients with peripheral thromboses, only the patient with a dorsal pedal artery occlusion had a significant problem (autoamputation of a toe). Although eight patients received L-asp subsequently without recurrence of the complication, two had transient neurological deterioration associated with the repeat administration of L-asp. Twenty-two patients received CNS prophylaxis consisting of intrathecal methotrexate, CNS radiation, or both, following the CNS event without deterioration. In general, clinical status was not compromised after thrombotic or hemorrhagic events. Although most patients had gross recovery of their neurological impairment, detailed neurological and neuropsychological testing is needed to elucidate possible defects.