OBJECTIVE There have been 15 published cases of probable pentamidine-induced torsade de pointes (TdP). A prospective analysis of this complication of therapy is valuable considering the high frequency of Pneumocystis carinii pneumonia in the AIDS population, and the role of pentamidine in its therapy. METHODS Open, nonrandomized, prospective study of HIV-infected patients receiving intravenous pentamidine in a 12-month period. METHODS Walter Reed Army Medical Center, a tertiary care, referral-based facility in Washington, DC. METHODS Eighteen HIV-infected patients were enrolled with informed consent; four were withdrawn from statistical analysis after receiving only one or two doses of empiric intravenously administered pentamidine. RESULTS Daily 12-lead electrocardiography, echocardiography, weekly signal-averaged electrocardiography, and weekly 24-h ambulatory electrocardiography were performed on each patient. Of the 14 subjects, 3 developed TdP. These 3 patients and 2 others developed a prolonged rate corrected, QT interval (QTc) to greater than 0.48 s (max QTc mean, 0.55 s, mean increase, 0.12 s). The QTc prolongation was noted in all five patients by the fourth daily dose (4 mg/kg/d) of pentamidine. The other 9 patients developed minimal change in QTc intervals throughout therapy (max QTc mean, 0.45 s; mean increase, 0.03 s). The maximum QTc increase was significantly different between these two cohorts (p < 0.03). The occurrence of TdP in the subgroup of patients developing prolonged QTc intervals to greater than 0.48 s (3 of 5 patients), or a change in QTc of greater than 0.08 s (3 of 4 patients) over individual baseline also was significant (p = 0.03 and p = 0.01, respectively). No baseline clinical variables associated with TdP or QTc prolongation were identified. CONCLUSIONS Intravenously administered pentamidine frequently results in QTc prolongation with a subsequent risk of TdP in HIV-infected patients. All patients treated with intravenously administered pentamidine should be evaluated with baseline and daily ECGs, at least during the first week of therapy, and should be closely monitored for a change in the QT interval. An increase in QTc to above 0.48 s or greater than 0.08 s above baseline carries a significant risk for proarrhythmia, and in this instance, continuous electrocardiographic monitoring or an alternative antibiotic regimen should be considered.