To evaluate the efficacy of bremelanotide (BMT) as a treatment for HSDD in premenopausal women. RECONNECT comprises 2 Phase 3 trials. The Core phase includes a 4-week screening period, a 4-week single-blind placebo period, and a 24-week double-blind period during which participants self-administered BMT (1.75 mg) or placebo subcutaneously using an auto-injector, as-needed, prior to sexual activity. Co-primary endpoints were change in the desire domain of the Female Sexual Function Index (FSFI-D) and the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) score for being bothered by low sexual desire (item 13). Secondary endpoints were change from baseline to end-of-study (EOS) in the FSFI total, arousal, lubrication, orgasm, and satisfaction scores; FSDS total and bother scores; Women's Index of Treatment Satisfaction (WITS-9) score; self-assessed benefit, and satisfying sexual event (SSE) items of the Female Sexual Encounter Profile-Revised (FSEP-R). The primary efficacy population comprises 1202 women (mean age 39 years; >80% white). The most frequent diagnosis was HSDD with decreased arousal. In both studies, women using BMT had significantly (P≤0.001) increased scores on the FSFI-D indicating an increase in desire and a significant (P≤0.01) reduction in their item 13 score on the FSDS-DAO indicating a reduction in distress related to low sexual desire. On secondary outcomes, BMT was associated with significant improvements from baseline to EOS in FSFI total, arousal, lubrication, orgasm, and satisfaction domain scores (all P≤0.01), FSDS total and bother scores (both P≤0.01), and WITS-9 and self-assessed benefit (both P<0.0001). FSEP-R scores for satisfaction with desire and arousal were significantly improved only in Study 301 (P≤0.01). Changes in the number of SSEs did not differ significantly from placebo; however, women taking BMT reported a higher percentage of sexual encounters as satisfactory. The most frequent AEs were nausea, flushing, and headache; most were mild or moderate. BMT's safety profile was consistent with prior experience.