Despite national recommendations for prophylactic group B streptococci intrapartum penicillin therapy (GBS-IPT), there is little guidance for clinicians regarding to how to achieve the recommended 4 hours of therapy. We sought to identify clinical triggers for effective temporal prompts to initiate GBS-IPT to achieve the recommended duration of therapy. GBS-colonized women who delivered between 37 and 42 weeks were analyzed retrospectively. The clinical record was reviewed for clinical events including rupture of membranes, oxytocin therapy, 4-cm dilation, active labor, narcotic analgesia, epidural analgesia. In addition, combinations of these triggers were evaluated using the first appearance of 4-cm dilation or active labor, narcotic analgesia or epidural, and a composite indicator of each of these four triggers. Antibiotic duration and proportion receiving 4 hours of GBS-IPT for each trigger were compared with the conventional penicillin management the patient actually received (CM). Data were analyzed with Z-test for proportions with Bonferroni correction and one-way analysis of variance. Two hundred thirteen women met study criteria and were reviewed. Using CM, 90.8% of nulliparas and 68.7% of parous women achieved adequate GBS-IPT. In nulliparas, each clinical trigger resulted in equivalent rates of adequate GBS-IPT compared with CM. The duration of therapy was less for 4-cm dilation, epidural, epidural or narcotic analgesia, and 4-cm dilation or active labor triggers in nulliparas, suggesting better identification of the period 4 hours prior to delivery. In parous women, clinical triggers did not perform better than CM. In nulliparous women, clinical triggers to initiate therapy may achieve high rates of GBS-IPT, with a significant decrease in the duration of antibiotic therapy. In nulliparous women, clinical triggers better identify the 4-hour window prior to delivery than CM.