The authors sought to determine whether neostigmine, given at a time when no response to peripheral nerve stimulation could be elicited, hastened recovery from a vecuronium-induced neuromuscular blockade (NMB). The effect of neostigmine (70 μg/kg) in antagonizing a profound (no-twitch) vecuronium-induced (0.1 mg/kg) NMB in 40 healthy patients was studied. Patients were randomly assigned to one of four groups specifying the sequence of neostigmine administration. Fifteen minutes after the administration of vecuronium, when there was no detectable twitch response, each patient received either neostigmine (70 μg/kg) with glycopyrrolate (15 μg/kg) or an equivalent volume of normal saline (placebo). When T1 (the first response in the train-of-four [TOF] sequence) recovered to 10% of control, patients again received either neostigmine with glycopyrrolate in the same doses as before or the placebo. The following variables were measured: times from vecuronium injection until T1 recovered to 10% (t [10]) and 90% (t [90]) of control, and time until the TOF ratio was equal to 75% (t [TOF75]). Mean values of t (90) and t (TOF75) were shorter (54.7–75.2 min and 60.4–79.5 min, respectively) for the three groups who received neostigmine as compared with patients who received two doses of placebo (104.3 and 122.6 min, respectively). There were no differences in the t (90) and t (TOF75) values among the three groups who received neostigmine. The authors concluded that the total time to achieve adequate recovery of neuromuscular function is the same whether neostigmine (70 μg/kg) is administered 15 min after vecuronium (0.1 mg/kg) or whether neostigmine is given when T1 has recovered to 10% of control. Furthermore, a second dose of neostigmine (70 μg/kg) neither hastens nor prolongs recovery. Thus, recovery time from a profound vecuronium-induced NMB can be shortened with the administration of neostigmine given before spontaneous recovery, and repeated administration of neostigmine does not alter the course of recovery.