Neuroleptic malignant syndrome (NMS) is a potentially lethal antipsychotic drug (APD)-induced thermoregulatory disturbance. We hypothesized that several precautionary measures taken after administeration of APDs might prevent progression to definite NMS. The study group included 657 consecutively admitted drug-free schizophrenia inpatients who received various typical APDs for 28 days. Specific predefined precautionary measures were employed for this group. The comparison group (n=192) consisted of typical APD-treated schizophrenia inpatients in whom such precautionary measures were not imposed. The study group exhibited a significantly lower incidence of definite NMS (1/657=0.2% versus 4/192=2.1%; P=0.01, odds ratio=13.96; 95% confidence interval 1.55-125.63). Antipsychotics were discontinued in 28 patients (28/657=4.3%) from the study group due to NMS (n=1) or early detection of potential NMS-related signs (probable abortive NMS) (n=27). Our findings suggest that specific precautionary measures can effectively reduce the incidence of definite NMS by approximately one order in newly medicated schizophrenia inpatients.