Anatomical characteristics, such as shallow vestibular depth, high frenum attachments, and thin labial bone tend to make treatment of mandibular gingival recession defects particularly challenging. Even though a number of recent systematic reviews have identified the connective tissue graft (CTG) in combination with coronally advanced flaps (CAF) as the most consistently effective treatment procedure for Miller Class I and II defects, they did not separate maxillary vs mandibular outcomes, reporting instead aggregate results. In this prospective consecutive case series, recombinant human platelet-derived growth factor-BB (rhPDGF-BB) was combined with CTGs for the treatment of Miller Class I or II mandibular gingival recession defects in 11 healthy patients. Changes for both mean recession depth and width from baseline to week 24 were statistically significant, with mean recession depth decreasing from 3.4 ± 0.5 mm to 0.8 ± 0.8 mm and mean recession width decreasing from 3.1 ± 0.7 mm to 1.7 ± 1.3 mm. As a result of the improvement in recession depth, the mean percent root coverage seen in this mandibular prospective consecutive case series at 6 months was 79.6%. Despite treatment results that were comparable to historical norms, the outcomes, especially percent root coverage at 24 weeks, were somewhat less favorable, emphasizing the anatomical challenges of mandibular recession defects.