Young women are particularly vulnerable for acquiring HIV yet they are often excluded from clinical trials testing new biomedical intervention. We assessed the HIV incidence and feasibility of enrolling a cohort of young women for potential participation in future clinical trials. Between March 2004 and May 2007, 594 HIV uninfected 14–30 year old women were enrolled into a longitudinal HIV risk reduction study in KwaZulu-Natal, South Africa. The overall HIV prevalence at screening in young girls below the age of 18 years was 27.6 % compared to 52.0 % in the women above 18 years, p<0.001. HIV incidence was 4.7 [95 % Confidence interval (CI) 1.5–10.9) and 6.9 (95 % CI 4.8–9.6)/100 women years (wy), p = 0.42 and pregnancy rates were 23.7 (95 % CI 14.9–35.9) and 16.4 (95 % CI 12.9–20.6)/100 wy, p = 0.29, in the women below and above 18 years respectively. Retention was similar in both groups (71.0 vs. 71.5 %, p = 0.90). This study demonstrates that the inclusion of young girls between the ages of 14 and 17 years in longitudinal studies is feasible and their inclusion in clinical trials would maintain scientific integrity and power of the study.