Introduction: Amniotic fluid provides the necessary fluid, space, and growth factors for fetal development. On the other hand, meconium-stained amniotic fluid causes a lot of neonatal morbidity and mortality. It also brings fetal distress syndrome, meconium aspiration syndrome, and ischemic encephalopathy. In spite of such alarming consequences, there have been few finding in Ethiopia in general and no study in Somali region in particular. Objective: To identify the determinants of meconium-stained amniotic fluid among laboring mothers in Jigjiga city health facilities, Somali region, Ethiopia, 2022. Method and materials: An institutional based unmatched case control study design was conducted in Jigjiga city health facilities from May1/2022 to June1/2022. The selected participants were 419 laboring mothers with 140 meconium-stained aspiration (cases), and 279 without meconium-stained amniotic fluid (controls) among laboring mothers. Data were collected using structured questionnaire through face-to-face interview, and chart record review using checklist. The collected data were entered Epi-data version 3.1 and export to version 16 for analysis. Logistic regression model was used for data analysis. Variable with P-value <0.25 in bivariable logistic regression analysis was transferred in to multi-variable logistic regression. Finally, statistically significant was declared at in multivariable logistic regression. Result: All 419 (140 cases and 279 controls) women were participated in the present study making the response rate of 100%. Preeclampsia [AOR=2.19, 95% CI: 1.070-4.48)], prolonged labor [AOR=1.869, 95% CI :( 1.03-3.392)], non-reassuring fetal heart rate [AOR = 1.825, 95% CI :( 1.066- 3.12)] and premature rupture of membrane [AOR =1.83, 95% CI (1.125-2.98)] were the independent determinants of Meconium-stained amniotic fluid in this study. Conclusion and Recommendation: Preeclampsia, non-reassuring fetal heart rate pattern, prolonged labor, and premature rupture of the membrane were independent determinants of meconium-stained amniotic fluid in the current study. Hence, early diagnosis and management of preeclampsia, early detection of progress of labor and monitoring of the fetus heart rate are effective for the prevention and to minimize the occurrence of meconium stained. Keywords: Meconium-stained amniotic fluid, determinants, Jigjiga city, Ethiopia. ABREVIATIONS AND ACRONYMS