In experimental studies, statin use has been associated with reduction of osteoclastic activity and promotion of bone formation around implants. Moreover, a large clinical study recently reported a substantially reduced risk of revision for aseptic loosening among statin users with THA. Our objective was to evaluate the influence of statin use on the development of femoral osteolysis within 5 years after THA. We conducted a case-cohort study including all THAs presenting with femoral osteolysis at the 5 year visit (cases) and compared them with those without osteolysis (controls). Cases and controls were identified from a cohort of primary THAs operated between 2001 and 2005. Seven hundred thirty-five THAs were included, mean age 68 years. Five years after surgery osteolysis had developed around the femoral component of 40 THAs (5.4%). Ever-use of statins was much less frequent among cases (5 of 40, 12.5%) than among controls (199 of 695, 28.6%). The crude risk ratio of femoral osteolysis among statin users was 0.36 (95% CI 0.14; 0.92). After adjusting for age, sex, activity level, BMI, diagnosis, bearing surface, and type of stem, the adjusted risk ratio was 0.38 (95% CI 0.15; 0.99). In conclusion, statin use was associated with a reduced risk of developing femoral osteolysis 5 years after THA. Statins may be useful for reducing the risk of implant failure following THA. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res