Background:Most women taking combined oral contraceptives (COCs) are satisfied with their contraceptive method. However, one of the most common reasons reported for discontinuation of combined oral contraceptives (COCs) is mood deterioration.Objectives:This study aimed to compare effects of the second and third generation oral contraceptive pills on the mood of reproductive women.Materials and Methods:This randomized, double-blind, controlled clinical trial was conducted in reproductive women at health centers in Tehran, Iran. Participants were randomized into the second and third generation oral contraceptive groups. Positive and negative moods were recorded using positive affect, negative affect scale (PANAS) tools at the end the second and fourth months of the study. Data analysis was carried out using ANOVA and P Values < 0.05 was considered significant.Results:Statistically significant difference was seen in positive and negative mood changes in women receiving contraceptive pills. The second generation oral contraceptive pills resulted in a decrease in positive mood (95% CI: 43.39 to 38.32 in second month and 43.39 to 26.05 in four month) and increase in negative mood (95% CI: 14.23 to 22.04 in second month and 14.23 to 32.26 in four month - P < 0.001), but the third generation led to an increase in positive mood (95% CI: 22.42 to 25.60 in second month and 22.42 to 33.87 in four month) and decrease in negative mood (95% CI: 36.78 to 31.97 in second month and 36.78 to 22.65 in four month - P < 0.001).Conclusions:Third generation combined oral contraceptive pills have a better effect on mood in women in reproductive ages than the second generation pills. It can be recommended as a proper combined oral contraceptive in Iran.