Background The aim of this study was to assess the efficacy, tolerability and safety of risedronate in adults with CF. Methods Patients with a lumbar spine (LS), total hip (TH) or femoral neck (FN) bone mineral density (BMD) Z-score of −1 or less were randomised to receive risedronate 35mg weekly or placebo, and calcium (1g)+vitamin D 3 (800IU). Results At baseline, BMD Z-scores in the risedronate (n=17) and placebo (n=19) groups were similar. By 24months, 7/17 risedronate patients vs 0/19 placebo patients stopped the study medication due to bone pain. After 24months treatment, the mean difference (95% CI) in change in LS, TH and FN BMD between the risedronate vs placebo groups was 4.3% (0.4, 8.2) p=0.03; 4.0% (−0.5, 8.6) p=0.08; and 2.4% (-3.5, 8.2) p=0.41. Conclusions After two years treatment there was a significant increase in LS BMD with weekly risedronate compared to placebo.