I occasionally have workbooks (xlsx/xlsm) that fail to save over the Network, getting a "File not saved" message, so I make sure that I 'save' first before closing the workbook instead of relying on the "Do you want to save.." option if I just close the workbook. For large files (40+ Mb), I frequently save, close, take a backup copy and the re-open the workbook.
You did not say which file type you are using but, if it is not .xlsb, you may want to consider trying that (note that some people appear to have encountered some limitations with that format). In the early days of Excel 2007 I found them to be smaller in size, faster (I believe) and less likely to become corrupt.