Background: Pre-clinical data demonstrate that aspirin inhibits tumour growth and prevents metastases. Meta-analyses of individual patient data from randomized trials evaluating cardiovascular (CV) effects of aspirin show reduced metastases and cancer deaths for those on aspirin. Toxicity concerns have limited aspirin use as a primary anti-cancer prevention agent. In the adjuvant setting, the risk:benefit ratio differs, with higher morbidity and mortality from recurrence potentially outweighing risks. Aspirin, an inexpensive drug with a potential therapeutic role in several common cancers, could have a large impact on the global cancer burden. The Add-Aspirin trial investigates if aspirin use after curative treatment for non-metastatic solid tumours prevents recurrence and prolongs survival. Methods: Add-Aspirin is a double blind, placebo-controlled, multicentre, international trial. Eligible participants (n=9,920) from the UK and India will have had potentially curative treatment for non-metastatic cancer. There are 4 separate tumour cohorts – breast (BC), colorectal (CRC), gastro-oesophageal (GOC) and prostate cancer (PC). Following an 8 week active run-in period of aspirin 100mg daily to assess adherence and tolerability, participants are randomised to aspirin 100mg, 300mg or placebo daily for > 5 years. Each tumour specific cohort is individually powered and has a separate disease-specific primary outcome measure: BC (n = 3,100) invasive disease-free survival (DFS); CRC (n = 2,600) DFS; GOC (n = 2,100) overall survival (OS); and PC (n = 2,120) biochemical recurrence-free survival. Secondary outcome measures include adherence, toxicity and CV events. OS across the 4 cohorts is a co-primary outcome measure. Sub-studies include assessment of thromboxane B2 for compliance and methodological work to assess the utility of long-term passive follow up. Blood/tissue specimens collected at enrolment will allow tumour-specific mutations to be used as stratification factors. Recruitment will commence by May 2014. Funder CRUK; Sponsor University College UK. Clinical trial information: 2013-004398-28.