I've had it happen a couple times over the last 7 years. Just moved on to different dosages or other PPI's or combinations. A couple of them lasted for a few years before they stopped working. Right now, I've tried them all (Prevacid, Protonix, Aciphex, Nexium, Zegrid, Prilosec, Kapidex) and none actually relieve my symptoms. I'm currently taking a double dose of Prevacid which for me is the "best of the worst". At least it helps a bit. Finally ended up with surgery because even on the PPI's, I was having serious reflux triggered breathing problems.