Oral Contraceptive Pills (OCP) are widely used by women of reproductive age and their use is increasing overtime. Yet, while OCPs have been shown to ameliorate mood symptoms in some women, mood changes are also commonly reported as side effects. The objective of this systematic literature review was to determine the effects of OCP on mood symptoms among healthy women using OCPs for contraception. We included prospective, longitudinal studies with clear comparison groups of either baseline versus post OCP use or case-control studies comparing women with or without OCP treatment. Despite the considerable variability in operational definitions of depression or negative affect, the majority of studies demonstrated no effect of OCP on depressive symptoms when compared with control or baseline data. While studies of manic symptoms were not available, irritability and mood swings related to the premenstrual phase were assessed. Results are equivocal with half the studies showing improvement in symptoms with OCP and half showing no difference. Overall, studies lacked standardized assessment tools and often relied on symptom checklists. Future research would benefit from the development and validation of a convenient tool for the assessment of mood symptoms across the menstrual cycle.