The present study investigated how students' self-efficacy changed after participation in four lab investigations that were designed on the basis of a new laboratory instructional strategy, namely, argument-driven inquiry (ADI). The study was conducted with 64 10th grade students from two intact classes in a public high school in the northeast of Turkey. One class was randomly assigned as an experimental group, and the other as a comparison group, and data were collected to allow for a comparison of students' self-efficacy across treatment conditions. Both experimental and control groups had the same chemistry courses and laboratories. However, the experimental group conducted laboratory activities that were designed using the ADI instructional model, and the control group performed traditional laboratory instruction. The Students Perceptions in Chemistry Evaluation (SPiCE) Instrument was used to measure students' perceptions of their own inquiry skills (self-efficacy) and attitudes about various aspects of chemistry. Additionally, the Interest in Science Pursuits Instrument was used to evaluate whether students' interest in pursuing science endeavors changed after their laboratory experience. The results indicate that the ADI instructional model improves students' perceptions about self-efficacy, inquiry skills, and lab skills as compared to traditional laboratory instruction. However, the findings showed that there was no significant difference between the experimental and the control group concerning students' attitudes toward chemistry. With regard to students' interest in pursuing science endeavors, there was also no significant difference between the experimental and the control groups.