Background/Objectives: Preterm birth remains a major cause of neonatal morbidity and mortality, particularly in multiple pregnancies and in cases of cervical shortening. While cervical cerclage is established in singleton pregnancies, its efficacy in multiple gestations remains uncertain. This study compares pregnancy and neonatal outcomes following second-trimester cerclage in singleton and multiple pregnancies with a short cervix. Methods: In this retrospective cohort study, 96 women underwent second-trimester cerclage at a tertiary perinatal center between 2020 and 2024. All had a cervical length ≤ 25 mm or prolapsed membranes without infection or premature rupture. Primary outcomes included term delivery rate, gestational age, mode of delivery, and neonatal outcomes; secondary outcomes comprised surgical complications and rehospitalization, defined as the need for renewed inpatient care due to threatened preterm labor or procedure-related complications. Results: In total, 79 singleton and 17 multiple pregnancies were analyzed. Term delivery occurred more often in singletons (54%) than multiples (18%, p = 0.006). Mean gestational age at birth was 258 ± 25 days in singletons versus 228 ± 28 days in multiples (p < 0.001). Birth weight was significantly lower in multiples (1985 g vs. 2943 g; p < 0.001), and neonatal infections were more frequent (53% vs. 26%; p = 0.008). Caesarean delivery was more common in multiples (82% vs. 33%; p < 0.001). Apart from increased postoperative contractions in multiples (24% vs. 5%; p = 0.031), complication rates and rehospitalization (27% vs. 29%; p = 0.8) were similar. Conclusions: Second-trimester cerclage is less effective in preventing preterm birth in multiple pregnancies compared to singleton pregnancies; however, it appears to be associated with a stabilizing clinical course and may facilitate outpatient management in selected high-risk cases. These findings support individualized counseling and shared decision-making, particularly in multifetal gestations.