Background The epidural analgesia technique is effective for labor analgesia and combinations of various local anesthetics with lipophilic opioids like fentanyl are used. However, fentanyl can cause an increased incidence of pruritus, urinary retention, nausea, vomiting, giddiness, shivering, and respiratory depression. Dexmedetomidine and clonidine are selective alpha 2 agonists with analgesic properties and have been used via the neuraxial route with local anesthetics for the same without the side effects of fentanyl. Thus, the primary objective was to assess and compare the analgesic efficacy of the two-drug combinations by the visual analog scale (VAS) score. Methods Fifty-four primigravida women were randomly allocated in two groups of 27 each and were given an initial bolus of 10 mL of 0.125% levobupivacaine with dexmedetomidine 0.5 ug/kg in Group A and with clonidine 1 μg/kg in Group B. Subsequently, each patient received a background infusion rate of 10 mL/h, a bolus dose of 5 ml, and a lock-out interval of 10 min via a patient-controlled-analgesia (PCA) pump. The blood pressure, heart rate, and severity of pain using VAS were assessed. Durations of the stages of labor, rate of instrumental delivery, and cesarean section, side effects, maternal sedation, and neonatal Apgar scores were also recorded. Results VAS scores in both the groups progressively decreased to <3 by 15 min with significant differences at five, 10, 15, and 120 min being lower in group A. Onset of analgesia and time for maximum analgesia was significantly shorter in group A. There was a significant decrease in hemodynamic parameters from baseline in both groups. The fall in heart rate was significantly greater in Group A and at almost all the time intervals after baseline, diastolic blood pressure (DBP) was also lower in group A. Maternal motor blockade scores, the intensity of maternal sedation, the incidence of maternal complications, the duration of the first and second stage of labor, the rate of instrumental delivery and cesarean section, total analgesic dose and PCA bolus requirement, and neonatal Apgar scores did not show a significant difference between the two groups. Conclusion Both dexmedetomidine and clonidine provide hemodynamically stable labor with a fall in heart rate and maternal blood pressure in the initial hours. Dexmedetomidine has the advantage of faster onset of analgesia and time for maximum analgesia.