Previous research suggests that the Relational Completion Procedure may be an effective alternative procedure for studying derived relational responding. However, the parameters that make it effective, relative to traditional match-to-sample, remain to be determined. The present experiment compared the Relational Completion Procedure and match-to-sample protocols for training and testing Same and Opposite derived stimulus relations. Trials to criterion and overall pass rate (i.e., yield) in both procedures were compared across three variables: presence versus absence of a confirmatory response requirement, three versus five comparison stimuli, and top-to-bottom versus left-to-right presentation format. Findings demonstrated a facilitative effect of the confirmatory response requirement in both procedures. Training trials to criterion were nominally but not significantly lower during the nonarbitrary training phase in the Relational Completion Procedure compared to match-to-sample, and the overall yield on the arbitrary relational test was greater in the former procedure compared to the latter. The present findings support the further development of the Relational Completion Procedure as an efficient alternative procedure for establishing Same and Opposite relations with adult humans, and with potential applicability to other types of derived relations.