Driveline infection is the most common infectious complication in patients with left ventricular assist devices. Minimum inhibitory concentration changes are not well described in relapsed driveline infections. This retrospective descriptive epidemiology study of patients with left ventricular assist device implantation between January 1, 2013, and August 1, 2017, who developed driveline infection with positive cultures aimed to describe minimum inhibitory concentration changes. Of the 330 patients underwent left ventricular assist device implantation, 30 (9%) met criteria for driveline infection. Median duration of follow-up was 26 months (interquartile range 16, 39) and time to first driveline infection was 171 days (interquartile range 83, 403). There were 74 driveline infections: 40 new and 34 relapsed. Staphylococcus aureus was most common in new and relapsed driveline infection. Thirteen patients comprised the 34 relapsed infections, 9 of which experienced a minimum inhibitory concentration change. Median time to first minimum inhibitory concentration change was 56 days (interquartile range 36-88), and type of minimum inhibitory concentration change was an increase in five cases, decrease in two cases, and both increase and decrease in two cases. Minimum inhibitory concentration changes did not result in resistance in S. aureus but did in Pseudomonas aeruginosa and Mycobacterium fortuitum relapsed driveline infection. Time to first relapse from initial infection was longer in those who received suppressive therapy, 60 days versus 83 days, p = 0.047. Relapsed driveline infections were most common with S. aureus. Minimum inhibitory concentration changes were quite variable and may not be the major contributor to relapsed infection in gram-positive driveline infection.