OBJECTIVES: Testosterone sales increased approximately 500% from 1993 to 2001. Despite this increase, only 5 percent of men with hypogonadism received appropriate treatment. Our study aimed to compare the characteristics of on-label and off-label testosterone use. METHODS: Characteristics of on-label, off-label, and indeterminate use were retrieved from IMS LifeLink Plus for 2006-2013 and compared. On-label and off-label indications and contraindications were identified using validated ICD-9-CM codes. Demographics, prescriber and payer types, comorbidities, contraindications, and off-label and on-label use were compared between user groups using Chi-square tests. RESULTS: A cohort of 48,493 incident testosterone users met our inclusion-exclusion criteria of which 12, 728 (26.3%) were on-label users, 5694 (11.7%) were off-label users and 30071 (62.0%) were indeterminate users. Females contributed a very small percentage among the on-label users (0.5%) but had a significant proportion among the off-label users (24.6%) and indeterminate users (15.7%). More on-label than off-label prescriptions were prescribed by general practice/family practice physicians (11.2% vs. 9.4%, p<0.0001). Conversely, more off-label than on-label prescriptions were written by OB/GYN (9% vs. 0.4%, p<0.0001). The most common on-label use was hypogonadism (99.8%), whereas the most common off-label use was decreased libido (53.4%). Prior prostate specific antigen testing was performed more frequently preceding on-label use (73.92%) as compared to off-label (48.3%) and indeterminate use (45.03%; p<0.0001). Similarly, serum testosterone concentration testing was also performed more frequently preceding on-label use (88.84%) as compared to off-label (75.08%) and indeterminate use (60.48%; p<0.0001). CONCLUSIONS: Characteristics of on-label and off-label users significantly differed in the commercially insured US population. Specific differences included gender, practitioner type, and prior testing.