Introduction. Substance use is one of the factors associated with lower condom use in young adults, which increases the likelihood of HIV infection. The Theory of Planned Behavior (TPB) is one of the most useful models for explaining this phenomenon since it considers the aim of engaging in a behavior based on attitudes, subjective norms and self-efficacy. Objective. To develop a questionnaire and to evaluate the Differential Item Functioning (DIF) caused by substance use in TPB indicators, using the Multiple Indicators Multiple Causes Analysis (MIMIC). Method. The study was conducted in two phases with Mexico City college students age 18 to 25. Results. Adequate goodness of fit was obtained in all three models of the TPB: attitudes χ2 S-B(2) = 3.902, p < .001; CFIs = .999; TLIs = .996; RMSEAs = .037, 90% CI ≤ .001-.095; subjective norms χ2 S-B(7) = 9.103, p < 0.245; CFIs = .999; TLIs = .998; RMSEAs = .022, 90% CI ≤ .001-.056; and self-efficacy χ2 S-B(25) = 65.115, p < .001; CFIs = .982; TLIs = .974; RMSEAs = .050, 90% CI = .036-.066; in one item in attitudes and two items in subjective norms a DIF effect was observed, while no item proved significant regarding self-efficacy. Discussion and conclusion. There is little evidence in the detection of DIF due to substance use in TPB indicators in condom use, and this is the first study to conduct this type of analysis. Items presenting DIF open the door to future research due to the importance of assessing how the indicator behaves with a population displaying a particular trait.