Objective: The aim of this study was to examine whether reaction time parameters in adult patients with ADHD could predict their response to methylphenidate (MPH). Method: Previously unmedicated patients (N = 123) were administered the Conners’ Continuous Performance Test II (CPT II) at baseline and after 6 weeks of treatment with immediate-release MPH. In addition to traditional CPT measures, we extracted intraindividual raw data and analyzed time series using linear and nonlinear mathematical models. Results: Clinical responders, assessed with the Clinical Global Impression-Improvement scale, showed significant normalization of target failures, reduced variability and skewness, and increased complexity of reaction time series after 6 weeks of treatment, while nonresponders showed no significant changes. Prior to treatment, responders had significantly higher variability and skewness, combined with lower complexity, compared with nonresponders. Conclusion: These results show that the CPT test is useful in the evaluation of treatment response to MPH.