<b><i>Introduction:</i></b> Loss-of-function mutation of <i>MKRN3</i> represents the most frequent genetic cause of familial central precocious puberty (CPP). The outcomes of gonadotropin-releasing hormone analog (GnRHa) treatment in CPP patients with <i>MKRN3</i> defects are unknown. <b><i>Objective:</i></b> To describe the clinical and hormonal features of patients with CPP with or without <i>MKRN3</i> mutations after GnRHa treatment. Anthropometric, metabolic and reproductive parameters were evaluated. <b><i>Patients and Methods:</i></b> Twenty-nine female patients with CPP due to loss-of-function mutations in the <i>MKRN3</i> and 43 female patients with idiopathic CPP were included. Their medical records were retrospectively evaluated for clinical, laboratory, and imaging study, before, during, and after GnRHa treatment. All patients with idiopathic CPP and 11 patients with CPP due to <i>MKRN3</i> defects reached final height (FH). <b><i>Results:</i></b> At the diagnosis, there were no significant differences between clinical and laboratory features of patients with CPP with or without <i>MKRN3</i> mutations. A high prevalence of overweight and obesity was observed in patients with CPP with or without <i>MKRN3</i> mutations (47.3 and 50%, respectively), followed by a significant reduction after GnRHa treatment. No significant differences in the values of mean FH and target height were found between the 2 CPP groups after GnRHa treatment. Menarche occurred at the expected age in patients with or without CPP due to <i>MKRN3</i> mutations (11.5 ± 1.3 and 12 ± 0.6 years, respectively). The prevalence of polycystic ovarian syndrome was 9.1% in patients with CPP due to <i>MKRN3</i> mutations and 5.9% in those with idiopathic CPP. <b><i>Conclusion:</i></b> Anthropometric, metabolic, and reproductive outcomes after GnRHa treatment were comparable in CPP patients, with or without <i>MKRN3</i> mutations, suggesting the absence of deleterious effects of <i>MKRN3</i> defects in young female adults’ life.