We previously demonstrated immune activation in the maternal peripheral circulation associated with preterm labor (PTL). There was an elevation in WBC mRNA of anti-inflammatory complement decay-accelerating factor (CD55) and the innate-immune response activating toll-like receptor 4 (TLR4). These findings suggested that collectively, these two molecules might serve as useful biomolecules to aid in the diagnosis of PTL. In this study, we used a combined marker approach to determine whether a dual marker model utilizing both CD55 and TLR4 mRNA levels to classify PTL would increase diagnostic accuracy compared to either molecule alone. Two methods were evaluated; a linear discriminant (LD) method and a distribution free (DF) method, in order to find the optimal linear combination of TLR4 and CD55 data to diagnose PTL accurately. Our results indicated that a combined CD55-TLR4 dual marker model could provide statistically significant improve- ments compared to CD55 or TLR4 single marker models for PTL classification performance.