Taking a test online rather than on paper is becoming increasingly common. However, there has been little research directly addressing the testing mode (taking a test on paper or online) in chemistry courses, particularly when students take multiple practice tests before an exam. Two studies were conducted to investigate student performance on two proctored general chemistry practice tests as a function of the testing mode. Data were collected in 2013 (Study 1) and again in 2015 (Study 2). The participants were 422 undergraduate students (Study 1 N = 207 and Study 2 N = 215) from a first-semester general chemistry course at a midwestern university. In each study students took two practice tests. Each test included 17 algorithmic, 5 conceptual, and 2 definition questions and was administered on computer or paper. The mode combination of Test 1–Test 2 identified the four conditions: Computer–Computer, Computer–Paper, Paper–Computer, and Paper–Paper. The results show minor differences between online and paper modes. In particular, no significant difference was found between Computer–Paper and Paper–Paper conditions. This pattern suggests that online testing is a promising alternative to the traditional paper-and-pencil mode most often used in chemistry.