The association between use of oral bisphosphonates and cancer development in elderly women is still uncertain, and previous studies have shown controversial results. We used a nationwide, population-based database to explore the relationship between the use of alendronate, an oral bisphosphonate agent used for the treatment of osteoporosis, and the risk of all malignancies in women with osteoporosis and age over 55 years. In the study group, we included 6906 women with osteoporosis (age, mean ± SD, 73.4 ± 8.4 years) taking oral alendronate, who were selected from a 1,000,000 sample cohort dataset collected between January 1998 and December 2009. Another 20,697 age- and comorbidity-matched women (73.5 ± 8.4 years) without bisphosphonates treatment were included in the control group. No subjects had any history of being diagnosed with cancer before inclusion. We used a log-rank test to analyze the differences in accumulated cancer-free survival rates between these two groups. A Cox proportional-hazard model, adjusted for confounding factors, was used to evaluate the association between alendronate use and the development of all cancer events in postmenopausal women with osteoporosis. During the mean follow-up period of 4.8 years, 821 patients from the study group and 2646 patients from the control group had new cancers. There was no significant difference in cancer incidence between alendronate users and controls (11.9% versus 12.8%, p = 0.054). The person-year incidence of newly-developed cancer in alendronate users and controls was 28.0 and 29.4 per 1000 person-years, respectively. Alendronate use was not associated with increased risk of cancer development in women with osteoporosis (adjusted hazard ratio, 1.05; 95% confidence interval [CI], 0.97–1.13; p = 0.237). However, due to the limited study size and underpowered results, further larger prospective studies or meta-analysis are suggested to further confirm our findings. © 2012 American Society for Bone and Mineral Research.