There is a lack of gender-specific research after reverse total shoulder arthroplasty (RTSA). Although previous studies have documented worse outcomes in women, a more thorough understanding of why outcomes may differ is needed. We therefore asked: (1) Are there gender-specific differences in preoperative and postoperative clinical scores, complications, surgery-related parameters, and demographics? (2) Is female gender an independent risk factor for poorer clinical outcomes after RTSA? (3) If so, why is female gender associated with poorer outcomes after RTSA? Between 2005 and 2019, 987 primary RTSAs were performed in our institution. After exclusion criteria were applied, data of 422 female and 271 male patients were analyzed. Clinical outcomes (absolute/relative Constant Score [a/rCS] and Subjective Shoulder Value [SSV]), complications (intra- and/or postoperative fracture, loosening), surgery-related parameters (indication, implant-related characteristics), and demographics (age, gender, body mass index, and number of previous surgeries) were evaluated. Preoperative and postoperative radiographs were analyzed (critical shoulder angle, deltoid-tuberosity index, reverse shoulder angle, lateralization shoulder angle, and distalization shoulder angle). Preoperative clinical scores (aCS, rCS, SSV, and pain level) and postoperative clinical outcomes (aCS and rCS) were significantly worse in women. However, the improvement between preoperative and postoperative outcomes was significantly higher in female patients for rCS (P=.037), internal rotation (P<.001), and regarding pain (P<.001). Female patients had a significantly higher number of intraoperative and postoperative fractures (24.9% vs. 11.4%, P<.001). The proportion of female patients with a deltoid-tuberosity index <1.4 was significantly higher than males (P=.01). Female gender was an independent negative predictor for postoperative rCS (P=.047, coefficient -0.084) and pain (P=.017, coefficient -0.574). In addition to female sex per se being a predictive factor of worse outcomes, females were significantly more likely to meet 2 of the 3 most significant predictive factors: (1) significantly worse preoperative clinical scores and (2) higher rate of intra- and/or postoperative fractures. Female sex is a very weak, but isolated, negative predictive factor that negatively affects the objective clinical outcome (rCS) after RTSA. However, differences did not reach the minimal clinically important difference, and it is not a predictor for the subjective outcome (SSV). The main reason for the worse outcome in female patients seems to be a combination of higher preoperative disability and higher incidence of fractures. To improve the outcome of women, all measures that contribute to the reduction of perioperative fracture risk should be used.