- Abstract Introduction The direction of the relationships between depression and sexual dissatisfaction is unclear. Possibly, these relationships are influenced by different elements/components of depression represented by different measures (i.e., Center for Epidemiologic Studies Depression Scale [CES-D], which highlights mood, vs. Beck Depression Inventory version II [BDI-II], which focuses on cognition and physical symptoms). High-achieving women—such as female medical students, interns, and residents—might be particularly prone to both depression and sexual dissatisfaction. Aim The aim of this study is to examine the direction of the longitudinal associations between depressive symptoms and sexual dissatisfaction in high-achieving, romantically involved female Israeli medical students and interns/residents using both CES-D and BDI-II. Methods One hundred ninety-four female medical students from the first, fourth, and seventh (internship) years from all medical schools in Israel who were currently involved in romantic relationships were assessed twice over a 1-year interval using both CES-D and BDI-II. Cross-lagged structural equation modeling analyses were employed. Main Outcome Measures Depressive symptoms were measured by the CES-D and the BDI-II. Sexual satisfaction was assessed by the “partner-satisfaction” factor of the Pinney Sexual Satisfaction Inventory. Results Elevated levels of CES-D-measured depression were found (26% at T1 and 13% at T2 above the stricter cutoff point). The direction of the longitudinal association between depressive symptoms and sexual dissatisfaction changed according to the depression measure used: baseline CES-D-measured depression predicted an increase in sexual dissatisfaction over time (β = 0.148, P = 0.016). Baseline sexual satisfaction predicted an increase in BDI-II-measured depression (β = 0.136, P = 0.045). Conclusion High-achieving, “fully-functioning” female medical students suffer from elevated levels of CES-D-measured depressed mood. Depressed mood might lead to sexual dissatisfaction, which in turn is likely to bring about “clinical,” BDI-II-measured depression. We recommend a routine assessment of depressed mood and sexual dissatisfaction in this population, as well as increased access to tailored intervention for both clinical challenges. Peleg-Sagy T and Shahar G. The prospective associations between depression and sexual satisfaction among female medical students. J Sex Med **;**:**–**.