In a retrospective case series study, medical records were evaluated for all male patients infected with human immunodeficiency virus (HIV) diagnosed over a one-year period with foot fractures (n = 30) confirmed by magnetic resonance imaging at a Los Angeles outpatient private practice rheumatology clinic. Proportionally more patients had received tenofovir prefracture (17 [57%]) than those who had not (13 [43%]). At fracture diagnosis, these two groups were similar in median age (49 versus 48 years), HIV-1 RNA (both 1.7 log(10) copies/mL), CD4 count (300 versus 364/mm(3)), time between HIV diagnosis and foot fracture (both 17 years), family history of degenerative bone disease (24% versus 23%), prevalence of malabsorption syndrome, renal failure, calcium deficiency, or vitamin D deficiency, and concurrent use of bisphosphonates, calcitonin, and diuretics. However, more tenofovir-treated patients had osteoporosis (35% versus 8%), stress-type fractures (53% versus 31%), concurrent fractures (12% versus 0%), wasting syndrome (29% versus 15%), truncal obesity (18% versus 8%), smoked cigarettes (more than one pack/day for more than one year; 35% versus 8%), dual energy X-ray absorptiometry (DEXA) T scores < -2.4 (denoting osteoporosis) at the femur (24% versus 9%) and spine (47% versus 36%), and had received protease inhibitors (71% versus 46%), non-nucleoside reverse transcriptase inhibitors (24% versus 0%), prednisone (24% versus 0%), testosterone (47% versus 23%), and teriparatide (29% versus 8%). Median time from tenofovir initiation until fracture was 2.57 (range 1.17-5.69) years. In conclusion, more foot fractures were observed in tenofovir-treated patients than in non-tenofovir-treated patients with HIV infection. Comorbidities and/or coadministered drugs may have been contributory.