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Objectives: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are potential candidates for chemoprevention of gastrointestinal cancer. We aimed to assess the association between contemporary NSAID use (≥180 days) and gastrointestinal cancer., Design: Nationwide Swedish population-based cohort study (2005-2012)., Setting: Sweden PARTICIPANTS: All adults exposed to maintenance NSAIDs use (aspirin, n=783 870; unselective NSAIDs, n=566 209, selective cyclo-oxygenase (COX)-2 inhibitors, n=17 948) compared with the Swedish background population of the same age, sex and calendar period., Outcome Measures: The risk of different gastrointestinal cancer types expressed as standardised incidence ratios (SIR) and 95% CIs, taking into account concurrent proton pump inhibitors (PPIs) and statins usage., Results: The SIR for gastrointestinal cancer for aspirin use was 1.02 (95% CI 1.00 to 1.04), with clearly reduced risk for long-term users (SIR=0.31, 95% CI 0.30 to 0.33 for 5.5-7.7 years), but an increased risk for short-term users (SIR=2.77, 95% CI 2.69 to 2.85), and stronger protective effect for low-dose aspirin (SIR=0.86, 95% CI 0.85 to 0.88). Users of non-selective NSAIDs showed an overall decreased risk of gastrointestinal cancer (SIR=0.79, 95% CI 0.77 to 0.82), in particular for cancer of the stomach, colorectum and oesophagus, and the SIRs were further decreased among long-term users. Users of selective COX-2 inhibitors showed a SIR=0.89 (95% CI 0.73 to 1.09) for gastrointestinal cancers. Both aspirin and unselective NSAIDs users who also were using PPIs, had higher risks for all gastrointestinal cancer types; and lower risk if using statins., Conclusion: Long-term use of (low-dose) aspirin and non-selective NSAIDs was associated with a decreased risk of all gastrointestinal cancer types., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)