<b><i>Aims:</i></b> Smoking cessation in subjects with a severe mental illness (SMI) is a challenging but attainable goal. Furthermore, the identification of variables involved in the quitting process is a highly relevant factor in clinical practice. This study aimed to analyze the influence of smokers’ motivation in smoking reduction and cessation and select the most suitable way of measuring motivation. <b><i>Methods:</i></b> This is a secondary analysis of a 9-month, multicenter trial examining a Multicomponent Smoking Cessation Program in 82 adult outpatients with SMI. At the end of the preparation stage, the smokers’ motivational level was evaluated with the University of Rhode Island Change Assessment Scale. This allowed us to rate subjects using a continuous measure (“Readiness to Change,” RTC) and group them in “Stages of Change” (SOC). Regression analyses were carried out to identify predictors of the efficacy outcomes: a reduction in at least 50% of the cigarettes smoked per day (CPD), a reduction in the expired carbon monoxide (CO), and complete abstinence from smoking. <b><i>Results:</i></b> We studied differences in measurements of motivational levels independently (RTC and SOC) for patients who had a reduction in at least 50% of the CPD and for patients who achieved complete abstinence from smoking. However, these differences did not reach statistical significance during the follow-up study with a logistic mixed-effects model. In a linear mixed-effects model, the reduction of expired CO was significantly associated with RTC, at the end of the active treatment phase and during follow-up (β: –1.51; SD 0.82; <i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> The motivation level achieved in the preparation phase predicted the reduction of expired CO over a given period when calculated by a continuous measure (RTC).