This study aimed to evaluate the effectiveness of the drug and violence resistance educational program (PROERD) on short-term secondary outcomes, such as intentions to use drugs, attitudes toward drugs, school experience, and life skills (refusal, decision-making, and communication). Two cluster-randomized controlled trials were conducted in 30 public schools in the city of São Paulo (Brazil) with 4030 students (1727 fifth and 2303 seventh graders). The intervention group attended 10 PROERD classes conducted by trained police officers, whereas the control group received no intervention. PROERD is a Brazilian adaptation of the North American Drug Abuse Resistance Education (DARE) program Keepin’ it REAL. Data were collected at two time points: pre-intervention and at 9-month follow-up. Two different paradigms were used in the multilevel analysis, complete case (CC), and intention-to-treat (ITT) analyses, using full information maximum likelihood (FIML). We found mixed results. Although the seventh-year curriculum seems to have positive effects on school experience (coef = 0.093; 95% CI: 0.001, −0.185), it also increases the intention to use cigarettes in the future (OR = 1.93, 95% CI: 1.109, 3.379) and the chances of accepting marijuana (OR = 1.62, 95% CI: 1.03, 2.53), and it appears to slightly reduce decision-making skills among fifth graders (coef = −0.078; 95% CI: −0.131, −0.025). Our results suggest that PROERD implementation and cultural adaptation should be reevaluated to understand why the program does not achieve the expected preventive goals and produces potential iatrogenic effects.