Purpose: Congress has identified the critical need to evaluate contributors to ongoing cancer drug shortages. Because increased competitionmayreduce drug shortages, weinvestigated the association between the number of suppliers for first-line breast, colon, and lung antineoplastics and drug shortages. Data and Methods: Using the 2003 to 2014 Red Book and national drug shortage data from the University of Utah's Drug Information Service, we used exploratory analysis to quantify time trends in first-line drug suppliers and shortages by cancer site. Generalized mixed models were used to examine the association between the number of suppliers for individual drugs and resulting drug shortages. Results: Among 35 antineoplastic drugs approved for first-line treatment of breast, colon, and lung cancer, the number of unique suppliers varied greatly (range, 1 to 19). In 2003, 12.5%, 33.3%, and 0% of breast, colon, and lung cancer drugs, respectively, experienced shortages, which increased overall by 2014, to 40.0%, 37.5%, and 54.5%, respectively. Having a small number of drug suppliers more than doubled the odds of shortages compared with a large number of suppliers (≥5), although the results were only statistically significant with three to four suppliers (odds ratio = 2.6, P =.049) but not with one to two suppliers (odds ratio = 3.49, P =.105). One of the strongest risk factors for drug shortages was the age of the drug, with older drugs significantly more likely to experience shortages (P <.001). Conclusion: Cancer drugs with a small number of suppliers had a higher risk of drug shortages than did those with ≥5 suppliers, but the relationship was nonlinear. Because the age of the drug is the strongest risk factor, future studies should explore underlying causes of shortages in older drugs.