A total of 5,495 HIV-negative women from KwaZulu-Natal, South Africa enrolled in three microbicide trials during the period of 2002--2008 were categorised as normal weight (body mass index (BMI: 18.6-<25), overweight (BMI: 25-<30) or obese (BMI: 30+). Incidence of HIV and other sexually transmitted infections such as Chlamydia and gonorrhoea were also estimated and compared by BMI groups. Combined data was analysed using STATA 10.0.Approximately 70% of the sample population was classified as being overweight or obese. Older age and lack of education were determined to be significant predictors of obesity. Women who were 35 years or older were more than three times as likely to be overweight and more than 12 times as likely to be obese compared to the youngest group. The highest HIV and STI incidence rates were observed among those with BMI <25 kg/m2 (normal weight) (8.1 and 19.8 per 100 person-year respectively) compared to women with BMI more than 25 kg/m2 (P<0.001, both).Effective obesity prevention strategies are needed to re-formulate HIV prevention programmes by incorporating healthy diet and life style messages to target those who are at highest risk not just for HIV infection but also for non-communicable diseases.