Tiotropium is a long-acting inhaled anticholinergic agent that is widely used in the treatment of chronic obstructive pulmonary disease (COPD). It was initially launched as the tiotropium HandiHaler formulation, but this was followed by a newer version based on a potentially more efficient drug delivery device, known as Respimat. This Respimat formulation is available worldwide but has not yet succeeded in gaining regulatory approval in the USA. In the past few years, the adverse effects profile of tiotropium has come under close scrutiny owing to concerns about the possibility of urinary and cardiovascular adverse effects. These concerns appeared to have been alleviated following the publication of data from the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, which was a large trial of 4 years’ duration. This trial did not show any excess myocardial infarction, renal or urinary adverse events with tiotropium compared with placebo. However, the risk of urinary retention has been in the spotlight again following publication of two observational studies reporting a significantly increased risk of urinary retention in men recently started on inhaled anticholinergics, especially when prostatic hyperplasia coexists. More recently, a meta-analysis of mortality data for the tiotropium Respimat formulation raised the possibility of an increased risk of death, including death from cardiovascular causes. It is unclear if the more efficient drug delivery offered by the Respimat device is hitting a different part of the dose-toxicity curve. In the absence of any evidence of superior clinical efficacy with tiotropium Respimat compared with tiotropium HandiHaler, some experts have argued that there is no compelling reason to choose the Respimat formulation given the new uncertainties about its safety profile.