Taiwan has never implemented supervised intermittent chemotherapy for pulmonary tuberculosis, and its application and results are unknown. The purpose of this study was to evaluate the efficacy and feasibility of a 62-dose, four-drug, 6-month, twice-weekly regimen administered by directly observed therapy for the treatment of pulmonary tuberculosis. Methods: From January 2004 through December 2006, a total of 116 patients with suspected or confirmed pulmonary tuberculosis were enrolled. Thirty-two of these patients were excluded from the analysis because of drug resistance, negative culture, self withdrawal and drug reactions. Isoniazid, rifampin, pyrazinamide, and ethambutol were administered daily for 2 weeks, followed by twice weekly at a higher dose for 6 weeks. Thereafter, isoniazid, ethambutol and rifampin were administered twice weekly for 18 weeks. Treatment was directly observed by nurses or outreach workers. Results: Of the 84 evaluable patients, 75 [89.3%, 95% confidence interval (CI): 80.6s–95.0%] patients were considered as successfully treated, three (3.6%, 95% CI: 0.7–10.1%) transferred out, five (6.0%, 95% CI: 2.0–13.3%) were unsuccessful and one (1.2%, 95% CI: 0.03–6.5%) died. Five patients were treatment failure (6.0%, 95% CI: 2.0–13.3%). Three patients had recurrences of pulmonary tuberculosis, and the recurrences were 4, 6 and 15 months after the completion of therapy. Sixpatients (5.2%) had severe adverse drug reactions and had their regimen modified. Conclusion: Prior to this study, intermittent therapy has not been attempted in Taiwan. This four-drug mostly twice-weeldy pulmonary tuberculosis treatment regimen is efficacious and relatively nontoxic, with a higher treatment success rate and a lower death rate. It considerably simplifies treatment and facilitates the execution of directly observed therapy. The reasons for the relatively high failure rate require further studies.