Background Gastroparesis (GP) is a chronic condition in which the stomach takes too long to empty its contents into the small intestine, despite the absence of any physical blockage. Females are generally more susceptible to developing GP than males. The objective of this study was to compare clinical outcomes between male and female patients hospitalized with GP using the Nationwide Inpatient Sample (NIS) database. Methods Using the NIS databases from 2020 to 2022 and the International Classification of Diseases, Tenth Edition Revision (ICD-10) codes, we performed a retrospective study of adult patients admitted with GP. We compared inpatient outcomes of GP between males and females. All-cause in-hospital mortality was the primary outcome. Secondary outcomes were total hospitalization cost adjusted to the year 2022, length of stay (LOS), incidence of sepsis, acute renal failure (ARF), shock, and need for intensive care unit (ICU) admission. We used STATA, version 16.1 (StataCorp LLC, College Station, TX), to perform the statistical analyses. Multivariate logistic regression analysis was conducted to assess whether gender was an independent predictor for these outcomes and to adjust for any confounders. Results It was noted that 31,114 adult patients were admitted for GP from 2020 to 2022; 23,886 (76.77%) were females, and 7,228 (23.23%) were males. The mean age of both males and females was 47.2 years. Males had a higher prevalence of diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), congestive heart failure (CHF), chronic kidney disease (CKD), and smoking/tobacco use. Females had a higher prevalence of prior cerebrovascular accident (CVA) and obesity. We found that female patients with GP had significantly longer LOS (+0.88 days, 95% CI: 0.53 - 1.29, P <0.01), higher total hospitalization costs (+$9,129.4, 95% CI: 4,946.0-13,312.7, P <0.01), and higher likelihood of venous thromboembolism (VTE) (adjusted odds ratio (aOR) 1.69, 95% CI: 0.83-3.44, P=0.147) as compared to males. Female patients had lower odds of developing sepsis (aOR: 0.60, 95% CI: 0.43-0.85, P <0.01), ARF (aOR 0.48, 95% CI: 0.41-0.56, P <0.01), shock (aOR: 0.54, 95% CI: 0.24-1.22, P=0.143), ICU admission (aOR 0.73, 95% CI: 0.57-0.92, P <0.01), and in-hospital mortality (aOR: 0.15, 95% CI: 0.05-0.45, P <0.01) as compared to males.  Conclusions We found that female patients had longer hospital LOS, total hospitalization charges, and a higher risk of VTE, while males had a higher risk of ARF, sepsis, shock, ICU admission, and all-cause in-hospital mortality. Although females are more frequently hospitalized for GP, males had significantly poorer clinical outcomes as compared to females. Our findings indicate that male patients with GP experience worse inpatient outcomes and require more aggressive treatment to reduce the risk of mortality and morbidity.