The study assessed effects of problem-based learning approach on senior secondary school students' practical skills in chemistry and the role of school type as a moderating variable. A pretest, posttest control group quasiexperimental setting with non-equivalent groups design was adopted. A total of 124 students (54 from coeducational and 70 from single-sex) of federal government colleges in Lagos and Oyo states of Nigeria participated in the study. A 33-item Chemistry Manipulative Skills Scale (CHEMMSS) with Cronbach alpha of 0.87 was used along with the treatment manuals as instruments. Findings show that students exposed to problem-based learning approach performed better in practical chemistry than those taught using conventional method. The result also revealed that students from single-sex colleges had higher mean score gain in practical skills in chemistry than those from coeducational colleges. Chemistry teachers are therefore enjoined to adopt problem-based learning approach in the teaching of practical chemistry and that teachers in coeducational schools should motivate and encourage their students so as to benefit meaningfully in the approach.