There are few studies on twins in Ecuador and Latin America. It requires a better understanding of perinatal conditions, especially from an ethnic perspective. This work aims to assess perinatal factors related to twin pregnancy in Ecuadorian Mestizo individuals. We performed an epidemiological, observational and cross-sectional study at the Hospital San Francisco and Hospital Nueva Aurora in Quito, Ecuador, from November 2019 to January 2020. It included 203 newborns from twin pregnancies, including mothers with and without pathological history. The average gestational age was 31 weeks, and the APGAR score at first minute was 6.86, with significant differences. Regarding the metabolic balance, the mean pH was 6.14; and bicarbonate was 11.57, with significant differences. Twins had intrauterine growth restriction in 6.9% of cases, with significant differences (p = .003); 81.4% required supplemental oxygen, with significant differences (p = .002); 93% required noninvasive mechanical ventilation (NIMV), with significant differences (p = . 003); 93% required inotropic and sedation, with substantial differences; 69% required antibiotics (≥21 days), with significant differences (p = .014); and 17.2% needed between 8 to 14 days of hospitalization, and 51% more than 28 days, with significant differences. The studied mothers’ demographic profile was mostly Mestizos, with an average age of 32 years, and 93% had a poverty status. Most of the twins were diamniotic monochorial and were discordant twins. It found jaundice, premature anemia and sepsis in 100% of twins and hyaline membrane disease in 89.66% of twins. Twins of women with relevant prenatal care had more premature births (30.4 ± 2.6 weeks), more acid−base imbalance, APGAR at ≥7 min in 90% of cases, and patent ductus arteriosus in all. There was also a greater need for double intensive phototherapy than twins of healthy women.