Patients using nonsteroidal anti-inflammatory drugs (NSAIDs) who are at high risk of gastroduodenal ulcer complications often do not receive gastroprotective co-therapy. Fixed-dose combination tablets of an NSAID and a proton-pump inhibitor or misoprostol are intended to improve adherence. Whether the use of these combination tablets will improve adherence and clinical outcome remains largely uninvestigated. Unlike proton-pump inhibitors and misoprostol, the efficacy of histamine-2-receptor antagonists in preventing gastroduodenal ulcers associated with NSAID use is questionable. Nonetheless, a new fixed-dose combination tablet of an NSAID and famotidine will soon be available on the market. The study by Laine et al. is a pooled analysis of two large-scale, carefully designed randomized trials (REDUCE trials) of a fixed-combination tablet of ibuprofen and famotidine on the incidence of endoscopic ulcers. How the study findings may influence clinical practice deserves further consideration.