Abstract Introduction Flibanserin possesses unique properties and displays selective agonistic and antagonistic activity against serotonin receptors. Originally, its primary application was in the treatment of hypoactive sexual desire disorder (HSDD) in women, where it showed promising results in improving sexual desire. However, as our understanding of its mechanism of action has expanded, researchers have begun to explore its potential utility in treating HSDD in males. This emerging trend has led to an increased interest in the use of flibanserin as a potential therapeutic option for men experiencing a decline in sexual desire. Objective We aimed to elucidate the demographic profiles, clinical attributes, and comprehensive safety implications of men receiving off-label flibanserin at our institution. Methods A retrospective analysis encompassing a cohort of men who initiated flibanserin treatment between July 2022 and July 2023 was performed. Basic demographic information, levels of total and free testosterone, pertinent medical history, scores from the International Index of Erectile Function (IIEF) and Patient Health Questionnaire-9 (PHQ-9), and overall manifestation of side effects were collected. Descriptive statistics were performed. Results A total of 26 patients were identified, with a mean age of 57.9 years (range, 31–80 years). Among these patients, seven had a prior diagnosis of depression and had previously received treatment with selective serotonin reuptake inhibitors (SSRIs). The mean levels of total testosterone and free testosterone were found to be 611.3 ng/dL and 116.8 pg/mL, respectively. Notably, a significant majority of patients (22 of 26 [81.4 %]) were diagnosed with erectile dysfunction. Importantly, all patients exhibited euthyroid status. The mean baseline score on the PHQ-9 was 5.30 (ranging, 0–17), indicating mild depressive symptoms, whereas the mean IIEF total score was 40 (range, 6–67). Furthermore, the mean score on the IIEF-desire subdomain was 5.65 (ranging: 2–10), reflecting relatively diminished levels of sexual desire. Upon conducting a follow-up assessment at the 3-month mark, it was observed that seven patients discontinued flibanserin medication, with reasons such as ineffectiveness and high cost being cited as the primary factors. Notably, only one patient (3.8%) discontinued the medication because of side effects. Conclusions In summary, our study sheds light on the fundamental characteristics associated with off-label utilization of flibanserin in men with HSDD, underscoring the increasing interest in investigating its potential therapeutic advantages within this specific population. However, additional research is warranted to comprehensively elucidate the clinical benefits and potential risks of flibanserin administration in men. Such investigations will contribute to a more thorough understanding of its efficacy and safety profile. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Disclosures: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast Investor: Sprout.