Rationale: Ipsilateral recurrence rates of spontaneous pneumothorax after video-assisted thoracoscopic surgery (VATS) are higher than the rates after open thoracotomy. Objectives: This study was conducted to determine if additional minocycline pleurodesis would be effective in diminishing recurrence after VATS treatment of primary spontaneous pneumothorax. Methods: Between June 2001 and February 2004, 202 patients with primary spontaneous pneumothorax were treated by conventional or needlescopic video-assisted thoracoscopic surgery. The procedures included resection of the blebs and mechanical pleurodesis by scrubbing the parietal pleura. After the operation, patients were randomly assigned to additional minocycline pleurodesis (103 patients) or to observation (99 patients). Main results: Patients in the minocycline group had higher intensity of chest pain and required more accumulated dose of meperidine injection. The short-term results showed that the two groups had comparable chest drainage duration, postoperative hospital stay, and complication rates. Patients in the minocycline group demonstrated a trend of decreased rate of prolonged air leaks (1.9% vs. 6.1%, p = 0.100). After a mean follow-up of 29 months (12 to 47 months), recurrent ipsilateral pneumothorax was noted in 2 patients in the minocycline group and 8 patients in the observation group (p = 0.044 by the Kaplan-Meier method and log-rank test). Postoperative long-term residual chest pain and pulmonary function were comparable in both groups. Conclusions: Although associated with intense immediate chest pain, additional minocycline pleurodesis is a safe and convenient procedure which can reduce the rate of ipsilateral recurrence after thoracoscopic treatment for primary spontaneous pneumothorax.