BACKGROUND:The use of oral contraceptives (OC) has been suggested to represent a potential risk factor for the development of obesity. However, the available literature assessing the relationship between OC use and the development of obesity is still scarce and characterised by controversial heterogeneity. We prospectively evaluated the association between the use of OC and the development of obesity in female participants of a middle-aged and free-living cohort. METHODS:The study population included 4920 female Spanish university graduates, initially nonobese women, with mean age (standard deviation) 28.2 (5.4) years. The study population was followed up for a mean of 8.6 (3.7) years. Self-reported use of OC and body mass index were assessed at baseline and biennially during follow-up. We used generalized estimating equation models to evaluate the association between exposure to OC and the development of obesity. RESULTS:After adjusting for potential confounders, baseline OC use was associated with higher odds of new-onset obesity during the full follow-up period (multivariable-adjusted odds ratio [OR] = 1.78; 95% Confidence Interval [CI]: 1.01-3.15). The continued use of OC for periods of time longer than 2 years was significantly associated with a higher risk of developing obesity (OR = 2.82, 95% CI: 1.17-6.82). CONCLUSIONS:According to our prospective cohort study, OC use is significantly associated with higher odds of obesity development, especially when the use of OC is steady and extends over periods of more than 2 years.