Health risk perception in smoking behavior was prospectively evaluated in a cluster-randomized trial for smoking cessation in Greek college students. Perceived Vulnerability (PV), Precaution Effectiveness, Optimistic Bias, and smoking behavior measures (quit attempts and cessation) were assessed in college-aged Greek student smokers at baseline, end of treatment (3 months), and follow-up (6 months). Using generalized estimating equations, baseline risk perception variables and change in risk perception variables between baseline and end of treatment were examined as predictors of the dichotomous smoking outcome variables. Results revealed that higher baseline PV [OR = 1.42 (1.21, 1.68)] predicted a greater likelihood of a quit attempt (n = 267). An increased likelihood of cessation [OR = 1.41 (1.15, 1.72)] was also predicted by an increase in PV from baseline to end of treatment (n = 243). Overall results suggested that PV was the strongest predictor of smoking behavior change, supporting further examination of health risk perceptions in promoting smoking cessation among Greek college smokers.