The aim of this study is to compare peri-operative outcomes for cesarean section (C-section) uterine closure with primary horizontal mattress suture to conventional single-layered running lock suture, with respect to estimated and quantitative operative blood loss, change in hemoglobin and hematocrit, length of hospital stay, and use of opioids for pain management during post-operative hospital admission. A retrospective cohort chart review was performed on patients undergoing elective primary or repeat cesarean section at a hospital in South Florida between January 2016 and August 2020. Of 506 included patients, 176 had primary horizontal mattress uterine closure completed by a single physician and 330 had conventional uterine closure completed by other physicians in the same hospital. None of the patients in either group were in labor or had spontaneous rupture of membranes. Demographic, clinical, and post-operative outcomes were collected from their operative note, post-operative note and progress note and then compared for each group. Baseline demographic and clinical features, including pre-pregnancy BMI, admission year, gravida, para, pre-surgery hemoglobin, and hematocrit were statistically similar. After adjusting for admission year, maternal age, and maternal race/ethnicity, the primary horizontal mattress closure demonstrated significantly lower estimated blood loss (EBL) (p<0.001) and smaller difference between pre- and post-c-section hemoglobin (p<0.027) and hematocrit (p<0.014) when compared to conventional closure methods. In addition, there was significant reduction in the length of total and post-surgical hospital stay (p<.001). There were no significant differences in quantitative blood loss (QBL) or percentage of patients using opioids during their hospital stay and no increase in infectious morbidity, need for blood transfusion. Post-cesarean section uterine closure with the single layered horizontal mattress suture technique provides a reasonable alternative during closure of hysterotomy leading to decreased operative blood loss, shorter duration of hospital stay, and reduction in opioid use for pain management. Although historically obstetricians perform a single-layered running lock uterine closure at the time of cesarean sections, our data supports that primary horizontal mattress uterine closure is a viable and effective option in providing an optimal post-operative course in patients undergoing a C-section. Prospective studies to confirm the value of uterine closure with the primary horizontal mattress are warranted.