Prior studies have identified self-regulatory strategies that are infrequently used by problem-gamblers, but which might be protective if used. However, guidelines with evidence-based safe gambling practices (SGPs) that prevent gambling-related harm are lacking. This study aimed to: 1) identify a parsimonious set of evidence-based SGPs that best predict non-harmful gambling amongst gamblers who are otherwise most susceptible to experiencing gambling harm; 2) examine how widely are they used; and 3) assess whether their use differs by gambler characteristics. A sample of 1,174 regular gamblers in Alberta Canada completed an online survey measuring uptake of 43 potential SGPs, gambling harms and numerous risk factors for harmful gambling. Elastic net regression identified a sub-sample of 577 gamblers most susceptible to gambling harm and therefore most likely to benefit from the uptake of SGPs. A second elastic net predicted gambling harm scores in the sub-sample, using the SGPs as candidate predictors. Nine SGPs best predicted non-harmful gambling amongst this sub-sample. The behaviour most strongly associated with increased harm was using credit to gamble. The behaviour most strongly associated with reduced harm was ‘If I’m not having fun gambling, I stop’. These SGPs form the basis of evidence-based safe gambling guidelines which can be: 1) promoted to consumers, 2) form the basis of self-assessment tests, 3) used to measure safe gambling at a population level, and 4) inform supportive changes to policy and practice. The guidelines advise gamblers to: stop if they are not having fun, keep a household budget, keep a dedicated gambling budget, have a fixed amount they can spend, engage in other leisure activities, avoid gambling when upset or depressed, not use credit for gambling, avoid gambling to make money, and not think that strategies can help you win. These guidelines are a promising initiative to help reduce gambling-related harm.