Define safe.
Life and death safe? You'll probably want to question why someone's life would be in the balanced based on the accuracy of your mapping data.
Practical day to day use safe? Absolutely. By definition, a mapping application needs to draw boundaries in some fashion or another. It's hard to draw a boundary for something that has no boundaries by definition (e.g. a P.O. box station).
For geolocation services such as store locators or distance calculators, it's a good practice to augment the ZCTA data with actual ZIP Codes if you can ascertain their locations. There are a variety of means, free and paid, that will help you do this ranging from Google Maps searches to Wolfram Alpha. Note that they tend to frown upon bulk searches or scraping. Both services have subscription geolocation lookup services.