diff --git a/lib/galaxy/datatypes/binary.py b/lib/galaxy/datatypes/binary.py
index 146447cb0e5c..1a7372f78ac8 100644
--- a/lib/galaxy/datatypes/binary.py
+++ b/lib/galaxy/datatypes/binary.py
@@ -552,22 +552,29 @@ class _BamOrSam:
     Helper class to set the metadata common to sam and bam files
     """
 
+    max_references = 100000
+
     def set_meta(self, dataset: DatasetProtocol, overwrite: bool = True, **kwd) -> None:
         try:
-            bam_file = pysam.AlignmentFile(dataset.get_file_name(), mode="rb")
-            # TODO: Reference names, lengths, read_groups and headers can become very large, truncate when necessary
-            dataset.metadata.reference_names = list(bam_file.references)
-            dataset.metadata.reference_lengths = list(bam_file.lengths)
-            dataset.metadata.bam_header = dict(bam_file.header.items())  # type: ignore [attr-defined]
-            dataset.metadata.read_groups = [
-                read_group["ID"] for read_group in dataset.metadata.bam_header.get("RG", []) if "ID" in read_group
-            ]
-            dataset.metadata.sort_order = dataset.metadata.bam_header.get("HD", {}).get("SO", None)
-            dataset.metadata.bam_version = dataset.metadata.bam_header.get("HD", {}).get("VN", None)
+            with pysam.AlignmentFile(dataset.get_file_name(), mode="rb", check_sq=False) as bam_file:
+                # TODO: Reference names, lengths, read_groups and headers can become very large, truncate when necessary
+                if bam_file.nreferences <= self.max_references:
+                    dataset.metadata.reference_names = list(bam_file.references)
+                    dataset.metadata.reference_lengths = list(bam_file.lengths)
+                    dataset.metadata.bam_header = dict(bam_file.header.items())  # type: ignore [attr-defined]
+                    dataset.metadata.read_groups = [
+                        read_group["ID"]
+                        for read_group in dataset.metadata.bam_header.get("RG", [])
+                        if "ID" in read_group
+                    ]
+                else:
+                    dataset.metadata.metadata_incomplete = True
+                dataset.metadata.sort_order = bam_file.header.get("HD", {}).get("SO", None)  # type: ignore [attr-defined]
+                dataset.metadata.bam_version = bam_file.header.get("HD", {}).get("VN", None)  # type: ignore [attr-defined]
         except Exception:
             # Per Dan, don't log here because doing so will cause datasets that
             # fail metadata to end in the error state
-            pass
+            dataset.metadata.metadata_incomplete = True
 
 
 class BamNative(CompressedArchive, _BamOrSam):
@@ -656,6 +663,16 @@ class BamNative(CompressedArchive, _BamOrSam):
         optional=True,
         no_value={},
     )
+    MetadataElement(
+        name="metadata_incomplete",
+        default=False,
+        desc="Indicates if metadata is incomplete",
+        param=MetadataParameter,
+        readonly=True,
+        visible=False,
+        optional=True,
+        no_value=False,
+    )
 
     def set_meta(self, dataset: DatasetProtocol, overwrite: bool = True, **kwd) -> None:
         _BamOrSam().set_meta(dataset, overwrite=overwrite, **kwd)
@@ -1054,7 +1071,7 @@ def dataset_content_needs_grooming(self, file_name: str) -> bool:
         """
         # The best way to ensure that BAM files are coordinate-sorted and indexable
         # is to actually index them.
-        with pysam.AlignmentFile(filename=file_name) as f:
+        with pysam.AlignmentFile(filename=file_name, check_sq=False) as f:
             # The only sure thing we know here is that the sort order can't be coordinate
             return f.header.get("HD", {}).get("SO") == "coordinate"  # type: ignore[attr-defined]
 
@@ -1074,7 +1091,7 @@ def dataset_content_needs_grooming(self, file_name: str) -> bool:
         """
         # The best way to ensure that BAM files are coordinate-sorted and indexable
         # is to actually index them.
-        with pysam.AlignmentFile(filename=file_name) as f:
+        with pysam.AlignmentFile(filename=file_name, check_sq=False) as f:
             return f.header.get("HD", {}).get("SO") != "queryname"  # type: ignore[attr-defined]