We aimed to verify the clinical and economic effects of uniportal video-assisted thoracic surgery (VATS) in patients with primary spontaneous pneumothorax (PSP) compared to traditional three-port VATS technique. We analyzed 51 consecutive patients (23 three-port VATS and 28 uni-port VATS), treated by bullectomy and pleural abrasion, to detect differences between the two groups with regard to intraoperative management, postoperative course, pain, paraesthesia and costs. Data about pain and paraesthesia were collected by telephonic interview within a minimum follow-up period of six months. Compared to three-port VATS, patients treated by the uni-port VATS were discharged more quickly (3.8 days vs. 4.9 days, P=0.03) and experienced paraesthesia less frequently (35% vs. 94%, P<0.0001). No difference in chronic pain was observed between the two groups (numeric pain score: 0.6 uni-port vs. 1.3 three-port, P=0.2). Compared to three-port VATS, we found a significant reduction in postoperative costs for the patients operated on by the uni-port technique (euro1407 vs. euro1793, P=0.03), without any increase in surgical costs. In conclusion, uniportal VATS appears to offer better clinical (postoperative stay and rate of paraesthesia) and economic (postoperative costs) results than the standard three-port VATS for treating primary spontaneous pneumothorax.