Aim The goal of the present study is to adopt state-of-the-art techniques and standards to develop and evaluate a measure, called the opposite-sex relationship questionnaire for female adolescents (OSRQFA), to assess the reasons why adolescent girls would or would not develop, a relationship with an adolescent boy. Methods A mixed-method, sequential, exploratory design was adopted. In the qualitative phase, an in-depth interview approach was used to identify the properties and dimensions to be included in the OSRQFA. In the quantitative phase, the psychometric properties of the OSRQFA were evaluated according to face, content and construct validity. Reliability and stability were assessed with Cronbach's α and test-retest analysis, respectively. Results A preliminary questionnaire including 86 items which emerged from the qualitative phase of the study was designed. Based on the impact scores for face validity and the cutoff points for the content validity ratio (CVR) and content validity index (CVI), the preliminary questionnaire was reduced to 57 items. The Kaiser criteria (eigenvalues >1) and scree plot tests demonstrated that 21 items forming six factors, which were labeled 'innate predilection', 'abstinence', 'peer pressure', 'fear of the relationship consequences', 'family atmosphere' and 'risk taking', that accounted for an estimated 66.19% of variance provided an optimal fit with the data. These scales had acceptable levels of internal consistency (α = 0.822) and stability (r = 0.871, p < 0.001). Conclusion The OSRQFA with 21 items and 6 factors demonstrated suitable validity and reliability in a sample of Iranian female adolescents. The OSRQFA's has good psychometric properties, and can be used by other researchers in future studies.