Because few tobacco withdrawal scales have been submitted to appropriate validity analyses, we sought to develop and assess the validity of a new, self-administered scale measuring cigarette withdrawal symptoms. We generated the instrument content by conducting a qualitative survey of 404 smokers and ex-smokers. Then we tested 61 items on the Internet in 3,050 smokers and ex-smokers. Subsamples provided comprehensive retest data after 17 days (n = 1218) and smoking status after 41 days (n = 673). The study resulted in a 21-item, six-dimension scale labeled the Cigarette Withdrawal Scale (CWS-21). The six subscales cover the main components of nicotine or tobacco withdrawal in the Diagnostic and Statistical Manual of Mental Disorders and International Statistical Classification of Diseases and Related Health Problems and in qualitative data: Depression-anxiety, craving, irritability-impatience, appetite-weight gain, insomnia, and difficulty concentrating. The six scores had a satisfactory test-retest reliability (r = .60-.71) and a high internal consistency (Cronbach's alpha = .83-.96). The factor structure of the scale was robust in a bootstrap resampling procedure. In ex-smokers, all scores except appetite-weight gain and insomnia predicted relapse at 41-day follow-up. In recent ex-smokers who had quit smoking less than 14 days before baseline, all scores except appetite-weight gain decreased between baseline and the 17-day retest. In baseline ex-smokers who relapsed to smoking at the 17-day retest, appetite-weight gain decreased and craving increased between baseline and retest. CWS-21 is a reliable, valid, multidimensional measure of cigarette withdrawal symptoms that is sensitive to change over time and predicts relapse to smoking.