To compare the efficacy of oral nifedipine and parenteral isoxsuprine in arresting preterm labor. Considering the paucity of studies comparing these two agents, a comparative analysis is obligatory. Eighty antenatal women in the gestational age range of 28-37 weeks, with regular uterine contractions, cervical dilatation ≤3 cm, and <50% cervical effacement, admitted with complaints of preterm labor pain were randomized to receive either 40 mg isoxsuprine or 20 mg nifedipine. Efficacy of the drugs was measured in terms of arrest of preterm labor, prolongation of pregnancy, and the days gained by infant before birth. Isoxsuprine showed increased lowering of systolic blood pressure (SBP), diastolic blood pressure (DBP), and slightly higher maternal pulse rate, but higher fetal pulse rate post-administration in comparison to nifedipine (P < 0.05). Isoxsuprine was significantly associated with more side effects. Pregnancy was more prolonged in the nifedipine group (25 days) than in the isoxsuprine group (19 days) (P < 0.05). The birth weight of neonates in group B was more than that of neonates in group A (P < 0.05). At 5 min after birth, none of the neonates in group B had an Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) abnormal score <7, compared to neonates in group A. Majority of neonates in group A showed tachycardia and respiratory distress syndrome (RDS) (17.5% and 12.5%, respectively), compared to group B (12.5% and 7.5%, respectively). The overall success rate was better in group B (86.8%) compared to group A (80%). Nifedipine was slightly more effective in arresting preterm labor with fewer side effects, compared to isoxsuprine.