Background: This case–control study compared the clinical outcomes of totally laparoscopic hemicolectomy with natural orifice specimen extraction (NOSE) and the conventional laparoscopically assisted approach for right‐sided colonic cancer. Methods: Consecutive patients who underwent totally laparoscopic mobilization of the right colon with transvaginal resection, anastomosis and specimen extraction between April 2007 and December 2009 were matched by various clinicopathological characteristics with patients who had conventional laparoscopically assisted procedures. Results: Thirty‐four patients in each group were studied. The number of lymph nodes harvested and the resection margin status were similar in the two groups. After NOSE, patients experienced less pain (mean(s.e.m.) pain score on day 1: 4·2(0·3) versus 5·7(0·3), P = 0·001; on day 3: 2·6(0·2) versus 3·5(0·2), P = 0·010) and had a shorter hospital stay (mean(s.d.) 7·9(0·8) versus 8·8(1·5) days; P = 0·003). The NOSE group had less surgical morbidity than the laparoscopically assisted group, but the difference was not significant (4 of 34 versus 9 of 34; P = 0·119). After a median follow‐up of 23 (range 5–40) months, there was no transvaginal access‐site recurrence or posterior colpotomy‐related complications. NOSE was associated with significantly better cosmetic results (mean(s.d.) score 7·5(1·7) versus 6·6(1·8); P = 0·037). Conclusion: The NOSE approach is feasible with favourable short‐term surgical outcomes. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Transvaginal access feasible