Background: Infertility is a worldwide problem affecting about 10% of couples. Hypothalamic- pituitary dysfunction due to Hyperprolactinemia is one of the leading causes of anovulatory infertility. However, there has been paucity of data on this subject in Sub-saharan Africa, hence, the need for this work. Objective: The purpose of this study was to determine the contribution of Hyperprolactinemia to female infertility in Calabar and also assess any association with bio-social factors and hypothyroidism. Methods: In this comparative cross sectional study, prolactin levels of 152 women in infertility clinics in Calabar were assessed. One hundred and thirty-three fertile subjects with similar age and socio-economic status were recruited from the family planning clinics and enrolled as controls. Prolactin measurement was performed using immunoassay auto-analyzer. Data were collected and analyzed using SPSS version 16.