Three settings are required on a programmed intermittent epidural bolus (PIEB) pump for labor analgesia: the PIEB next bolus (PIEBnb), PIEB interval (PIEBi), and PIEB volume (PIEBv). The ideal settings for these parameters are still unknown. We hypothesized a mathematical modeling tool, response surface methodology (RSM), could estimate 3 PIEB pump parameters while balancing 3 clinically important patient outcomes simultaneously. The study objective was to use RSM to estimate PIEB settings (PIEBnb, PIEBi, and PIEBv) while maximizing maternal satisfaction, minimizing the need for clinician-administered boluses, and optimizing the ratio of delivered/requested patient-controlled epidural analgesia (PCEA) boluses simultaneously. With institutional ethics approval, a double-blind randomized trial was completed in a tertiary care labor and delivery center. Nulliparous, English-speaking American Society of Anesthesiologists (ASA) physical status II patients aged 18 to 45 years at full term, single gestation in vertex presentation, in spontaneous labor and ≤7 cm cervical dilation were included. Patients with comorbidities, contraindications to neuraxial analgesia, using chronic analgesics, <152 cm, or body mass index (BMI) >45 kg/m 2 were excluded. After informed consent, labor analgesia was initiated using 10 mL ropivacaine 0.2% with 10 µg/mL fentanyl solution and PCEA (volume 6 mL every 10 minutes). Patients were randomized to predetermined PIEB settings. RSM identified 3 pump settings that represented a stationary point that best maximized or minimized 3 outcomes simultaneously: PCEA ratio (a ratio closest to 1), clinician bolus (optimal is 0), and maternal satisfaction (visual analog scale, 0-100, ideal response is ≥90). Of 287 potential participants, 192 did not meet inclusion criteria or declined to participate, and 26 were withdrawn, leaving 69 patients for study inclusion. Using RSM, the suggested PIEB settings for all the primary study outcomes were as follows: PIEBnb = 29.4 minutes, PIEBi = 59.8 minutes, and PIEBv = 6.2 mL. These PIEB settings corresponded to the following clinical outcomes: maternal satisfaction at 93.9%, PCEA ratio at 0.77, and need for clinician bolus at 0.29. The dermatome sensory score was between T10 and T5 in 89% of the patients. The median lowest Bromage score was 4. This novel study used a mathematical model to estimate PIEB pump settings while simultaneously maximizing 3 clinical outcomes. Equally weighted clinical outcomes prevent maximal outcome optimization and may not reflect patient priorities. Future studies or quality improvement endeavors could use RSM methodology to estimate PIEB pump settings targeting optimal values for a single clinical outcome of determined importance to parturients.