A nonequivalent, control group design was used to investigate student achievement in secondary chemistry. This study investigated the effect of process-oriented guided inquiry learning (POGIL) in high school chemistry to reduce alternate conceptions related to the particulate nature of matter versus traditional lecture pedagogy. Data were collected from chemistry students in four large high schools and were analyzed using analysis of covariance. The results show that POGIL pedagogy, as opposed to traditional lecture pedagogy, resulted in fewer alternate conceptions related to the particulate nature of matter. Male and female students in the POGIL group posted better posttest scores than their traditional group peers. African-American and Hispanic students in the POGIL group exhibited achievement gains consistent with Caucasian and Asian students. Further studies are needed to determine the value of POGIL to address achievement gap concerns in chemistry.